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Pienar C, Pop L, Lăzărescu M, Costăchescu R, Mogoi M, Mare R, Șeclăman E. Genetic Predisposition to Primary Lactose Intolerance Does Not Influence Dairy Intake and Health-Related Quality of Life in Romanian Children: A Hospital-Based Cross-Sectional Study. CHILDREN (BASEL, SWITZERLAND) 2023; 10:1075. [PMID: 37371306 DOI: 10.3390/children10061075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Revised: 06/11/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023]
Abstract
BACKGROUND Primary lactose intolerance (PLI) is characterized by the inability to digest lactose. Homozygotes for the lactase gene polymorphisms (CC or GG) are considered to be genetically predisposed to PLI. Still, symptoms may only be present later in life. The evidence supporting a link between PLI, dairy intake, and quality of life (QoL) is limited in children. AIM This study investigates the link between LCT polymorphisms and suggestive symptoms and the influence of the genetic predisposition to PLI on dairy intake and QoL in Romanian children. MATERIALS AND METHODS We recruited consecutive children evaluated in our ambulatory clinic. We asked all participants to complete a visual-analog symptoms scale, a dairy intake, and a QoL questionnaire. We used strip genotyping to identify genetic predisposition to PLI. RESULTS 51.7% of children had a CC genotype, and 34.5% also had a GG genotype. Most children reported no or mild symptoms. Dairy intake and QoL were similar across study groups. CONCLUSIONS Our study shows that genetic predisposition does not necessarily assume the presence of specific symptoms. Genetic predisposition to PLI did not lead to dairy avoidance, nor did it negatively influence our children's QoL.
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Affiliation(s)
- Corina Pienar
- Department of Pediatrics, 2nd Pediatrics Clinic, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Liviu Pop
- Department of Pediatrics, 2nd Pediatrics Clinic, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Marilena Lăzărescu
- The Necker-Enfants Malades Hospital, University of Paris Descartes, 75006 Paris, France
| | - Radmila Costăchescu
- Department of Pediatrics, 2nd Pediatrics Clinic, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Mirela Mogoi
- Department of Pediatrics, 2nd Pediatrics Clinic, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Ruxandra Mare
- Gastroenterology Department, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Edward Șeclăman
- Biochemistry Department, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania
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Marabotto E, Ferone D, Sheijani AD, Vera L, Ziola S, Savarino E, Bodini G, Furnari M, Zentilin P, Savarino V, Giusti M, Navarro Rojas FA, Bagnasco M, Albertelli M, Giannini EG. Prevalence of Lactose Intolerance in Patients with Hashimoto Thyroiditis and Impact on LT4 Replacement Dose. Nutrients 2022; 14:nu14153017. [PMID: 35893871 PMCID: PMC9331471 DOI: 10.3390/nu14153017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/11/2022] [Accepted: 07/15/2022] [Indexed: 11/16/2022] Open
Abstract
Purpose: to determine lactose intolerance (LI) prevalence in women with Hashimoto’s thyroiditis (HT) and assess the impact of LI on LT4 replacement dose. Methods. consecutive patients with HT underwent Lactose Breath Test and clinical/laboratory data collection. Unrelated gastrointestinal disorders were carefully ruled out. Lactose-free diet and shift to lactose-free LT4 were proposed to patients with LI. Results: we enrolled 58 females (age range, 23−72 years) with diagnosis of HT. In total, 15 patients were euthyroid without treatment, and 43 (74%) euthyroid under LT4 (30 of them with a LT4 formulation containing lactose). Gastrointestinal symptoms were present in 84.5% of patients, with a greater prevalence in change in bowel habits in lactose-intolerant patients (p < 0.0001). The cumulative LT4 dose required did not differ in patients with or without LI. No significant difference in both TSH values and LT4 dose were observed in patients shifted to lactose-free LT4 and diet at 3 and 6 months compared to baseline. Conclusion: the prevalence of LI in patients with HT was 58.6%, not different from global prevalence of LI. In the absence of other gastrointestinal disorders, LI seems not to be a major cause of LT4 malabsorption and does not affect the LT4 required dose in HT patients.
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Affiliation(s)
- Elisa Marabotto
- Division of Gastroenterology, Department of Internal Medicine (DiMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (G.B.); (M.F.); (P.Z.); (V.S.); (E.G.G.)
| | - Diego Ferone
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, Viale Benedetto XV, 16132 Genoa, Italy; (D.F.); (L.V.); (M.G.); (F.A.N.R.); (M.B.)
| | - Afscin Djahandideh Sheijani
- Division of Gastroenterology, Department of Internal Medicine (DiMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (G.B.); (M.F.); (P.Z.); (V.S.); (E.G.G.)
| | - Lara Vera
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, Viale Benedetto XV, 16132 Genoa, Italy; (D.F.); (L.V.); (M.G.); (F.A.N.R.); (M.B.)
| | - Sebastiano Ziola
- Division of Gastroenterology, Department of Internal Medicine (DiMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (G.B.); (M.F.); (P.Z.); (V.S.); (E.G.G.)
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy;
| | - Giorgia Bodini
- Division of Gastroenterology, Department of Internal Medicine (DiMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (G.B.); (M.F.); (P.Z.); (V.S.); (E.G.G.)
| | - Manuele Furnari
- Division of Gastroenterology, Department of Internal Medicine (DiMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (G.B.); (M.F.); (P.Z.); (V.S.); (E.G.G.)
| | - Patrizia Zentilin
- Division of Gastroenterology, Department of Internal Medicine (DiMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (G.B.); (M.F.); (P.Z.); (V.S.); (E.G.G.)
| | - Vincenzo Savarino
- Division of Gastroenterology, Department of Internal Medicine (DiMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (G.B.); (M.F.); (P.Z.); (V.S.); (E.G.G.)
| | - Massimo Giusti
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, Viale Benedetto XV, 16132 Genoa, Italy; (D.F.); (L.V.); (M.G.); (F.A.N.R.); (M.B.)
| | - Fabiola Andrea Navarro Rojas
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, Viale Benedetto XV, 16132 Genoa, Italy; (D.F.); (L.V.); (M.G.); (F.A.N.R.); (M.B.)
| | - Marcello Bagnasco
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, Viale Benedetto XV, 16132 Genoa, Italy; (D.F.); (L.V.); (M.G.); (F.A.N.R.); (M.B.)
| | - Manuela Albertelli
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, Viale Benedetto XV, 16132 Genoa, Italy; (D.F.); (L.V.); (M.G.); (F.A.N.R.); (M.B.)
- Correspondence:
| | - Edoardo G. Giannini
- Division of Gastroenterology, Department of Internal Medicine (DiMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (G.B.); (M.F.); (P.Z.); (V.S.); (E.G.G.)
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Hammer HF, Fox MR, Keller J, Salvatore S, Basilisco G, Hammer J, Lopetuso L, Benninga M, Borrelli O, Dumitrascu D, Hauser B, Herszenyi L, Nakov R, Pohl D, Thapar N, Sonyi M. European guideline on indications, performance, and clinical impact of hydrogen and methane breath tests in adult and pediatric patients: European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Neurogastroenterology and Motility, and European Society for Paediatric Gastroenterology Hepatology and Nutrition consensus. United European Gastroenterol J 2022; 10:15-40. [PMID: 34431620 PMCID: PMC8830282 DOI: 10.1002/ueg2.12133] [Citation(s) in RCA: 75] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 06/18/2021] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION Measurement of breath hydrogen (H2 ) and methane (CH4 ) excretion after ingestion of test-carbohydrates is used for different diagnostic purposes. There is a lack of standardization among centers performing these tests and this, together with recent technical developments and evidence from clinical studies, highlight the need for a European guideline. METHODS This consensus-based clinical practice guideline defines the clinical indications, performance, and interpretation of H2 -CH4 -breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 44 experts from 18 European countries. Eighty eight statements and recommendations were drafted based on a review of the literature. Consensus (≥80% agreement) was reached for 82. Quality of evidence was evaluated using validated criteria. RESULTS The guideline incorporates new insights into the role of symptom assessment to diagnose carbohydrate (e.g., lactose) intolerances and recommends that breath tests for carbohydrate malabsorption require additional validated concurrent symptom evaluation to establish carbohydrate intolerance. Regarding the use of breath tests for the evaluation of oro-cecal transit time and suspected small bowel bacterial overgrowth, this guideline highlights confounding factors associated with the interpretation of H2 -CH4 -breath tests in these indications and recommends approaches to mitigate these issues. CONCLUSION This clinical practice guideline should facilitate pan-European harmonization of diagnostic approaches to symptoms and disorders, which are very common in specialist and primary care gastroenterology practice, both in adult and pediatric patients. In addition, it identifies areas of future research needs to clarify diagnostic and therapeutic approaches.
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Affiliation(s)
- Heinz F. Hammer
- Division of Gastroenterology and HepatologyDepartment of Internal MedicineMedical UniversityGrazAustria
| | - Mark R. Fox
- Centre for Integrative GastroenterologyDigestive Function: BaselLaboratory and Clinic for Motility Disorders and Functional Gastrointestinal DiseasesKlinik ArlesheimArlesheimSwitzerland
- Division of Gastroenterology and HepatologyUniversity Hospital ZurichZurichSwitzerland
| | - Jutta Keller
- Department of Internal MedicineIsraelitic HospitalAcademic Hospital of the University of HamburgHamburgGermany
| | - Silvia Salvatore
- Pediatric DepartmentHospital “F. Del Ponte”University of InsubriaVareseItaly
| | - Guido Basilisco
- Gastroenterology and Endoscopy UnitFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanoItaly
| | - Johann Hammer
- Department of Gastroenterology and HepatologyUniversity Hospital of Internal Medicine 3Medical University of ViennaViennaAustria
| | - Loris Lopetuso
- UOC Medicina Interna e GastroenterologiaDipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico Universitario A. Gemelli IRCCSRomeItalia
- Department of Medicine and Ageing Sciences“G. d'Annunzio” University of Chieti‐PescaraChietiItaly
| | - Marc Benninga
- Department of Pediatric Gastroenterology, Hepatology and NutritionEmma Children's HospitalAmsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands
| | - Osvaldo Borrelli
- UCL Great Ormond Street Institute of Child Health and Department of GastroenterologyNeurogastroenterology and MotilityGreat Ormond Street HospitalLondonUK
| | - Dan Dumitrascu
- Department of GastroenterologyClinica Medicala 2Cluj‐NapocaRomania
| | - Bruno Hauser
- Department of Paediatric Gastroenterology, Hepatology and NutritionKidZ Health Castle UZ BrusselBrusselsBelgium
| | - Laszlo Herszenyi
- Department of GastroenterologyMedical CentreHungarian Defence ForcesBudapestHungary
| | - Radislav Nakov
- Clinic of GastroenterologyTsaritsa Yoanna University HospitalMedical University of SofiaSofiaBulgaria
| | - Daniel Pohl
- Division of Gastroenterology and HepatologyUniversity Hospital ZurichZurichSwitzerland
| | - Nikhil Thapar
- UCL Great Ormond Street Institute of Child Health and Department of GastroenterologyNeurogastroenterology and MotilityGreat Ormond Street HospitalLondonUK
- Gastroenterology, Hepatology and Liver TransplantQueensland Children's HospitalBrisbaneAustralia
| | - Marc Sonyi
- Division of Gastroenterology and HepatologyDepartment of Internal MedicineMedical UniversityGrazAustria
- Clinic for General Medicine, Gastroenterology, and Infectious DiseasesAugustinerinnen HospitalCologneGermany
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Rocco A, Compare D, Sgamato C, Martino A, De Simone L, Coccoli P, Melone ML, Nardone G. Blinded Oral Challenges with Lactose and Placebo Accurately Diagnose Lactose Intolerance: A Real-Life Study. Nutrients 2021; 13:nu13051653. [PMID: 34068318 PMCID: PMC8153320 DOI: 10.3390/nu13051653] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/05/2021] [Accepted: 05/10/2021] [Indexed: 02/07/2023] Open
Abstract
Lactose intolerance (LI) is characterized by diarrhea, abdominal pain, or bloating occurring after lactose consumption in patients with lactose malabsorption. The National Institute of Health (NIH) proposed a double-blind placebo testing to identify LI individuals correctly. However, until now, no study used this approach in a real-life setting. We aimed to assess double-blind placebo challenge accuracy in diagnosing LI in patients with self-reported symptoms of LI. 148 patients with self-reported LI were consecutively enrolled and blindly underwent hydrogen breath test (HBT) after 25 g lactose or 1 g glucose (placebo) load. One week later, the subjects were challenged with the alternative substrate. Each subject completed a validated questionnaire, including five symptoms (diarrhea, abdominal pain, vomiting, bowel sounds, and bloating) scored on a 10-cm visual analog scale. Home questionnaire (HQ) referred to symptoms associated with the consumption of dairy products at home, while lactose questionnaire (LQ) and placebo questionnaire (PQ) referred to symptoms perceived throughout the 4-h after the administration of the substrates, respectively. After lactose load, HBT was positive in 81 patients (55%), of whom 60 (74%) reported relevant symptoms at LQ (lactose malabsorbers, LM). After placebo challenge, 45 out of 60 with a positive lactose challenge did not complain of symptoms and therefore were diagnosed as lactose intolerant, according to NIH definition. The blinded oral challenges with lactose and placebo accurately diagnose LI and identify patients who will likely benefit from a lactose-free diet.
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Katoch GK, Nain N, Kaur S, Rasane P. Lactose Intolerance and Its Dietary Management: An Update. J Am Coll Nutr 2021; 41:424-434. [PMID: 33831336 DOI: 10.1080/07315724.2021.1891587] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Milk is the most common food consumed worldwide and is also a major ingredient in the preparation of various dairy products. However, despite the high production and consumption of milk and milk-based products, there is a large percent of the world's population that suffer from allergies to milk solids and lactose intolerance. Lactose intolerance specifically means the inability of the body to breakdown the sugar to its simplest form for assimilation and it is due to the inefficiency or lack of the enzyme in the human body. The most convenient prevention method for the affected population is to avoid milk and milk-based products but this may be a cause of development of other health related issues that result from inadequate nutrient consumption. To help find an alternative to this problem, this study aims at first studying the underlying information on lactose intolerance and then studying plant-based beverages as a possible alternative to milk and milk-based products. Key teaching pointsLactose intolerance specifically means the inability of the body to breakdown the sugar to its simplest form for assimilation and it is due to the inefficiency or lack of the enzyme in the human body.Consumption of probiotics may help relieve the symptoms of lactose intolerance.Soy beverage can be an economical alternative for lactose intolerant populations and has calcium content comparable to bovine milk.Calcium absorption in fortified plant based beverages depends upon type of calcium salt used.
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Affiliation(s)
- Gunjan Kumari Katoch
- Department of Food Technology and Nutrition, Lovely Professional University, Phagwara, India
| | - Neegam Nain
- Department of Food Technology and Nutrition, Lovely Professional University, Phagwara, India
| | - Sawinder Kaur
- Department of Food Technology and Nutrition, Lovely Professional University, Phagwara, India
| | - Prasad Rasane
- Department of Food Technology and Nutrition, Lovely Professional University, Phagwara, India
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Seoane RG, Garcia-Recio V, Garrosa M, Rojo MÁ, Jiménez P, Girbés T, Cordoba-Diaz M, Cordoba-Diaz D. Human Health Effects of Lactose Consumption as a Food and Drug Ingredient. Curr Pharm Des 2020; 26:1778-1789. [PMID: 32048961 DOI: 10.2174/1381612826666200212114843] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 01/01/2020] [Indexed: 02/07/2023]
Abstract
Lactose is a reducing sugar consisting of galactose and glucose, linked by a β (1→4) glycosidic bond, considered as an antioxidant due to its α-hydroxycarbonyl group. Lactose is widely ingested through the milk and other unfermented dairy products and is considered to be one of the primary foods. On the other hand, lactose is also considered as one of the most widely used excipients for the development of pharmaceutical formulations. In this sense, lactose has been related to numerous drug-excipient or drug-food pharmacokinetic interactions. Intolerance, maldigestion and malabsorption of carbohydrates are common disorders in clinical practice, with lactose-intolerance being the most frequently diagnosed, afflicting 10% of the world's population. Four clinical subtypes of lactose intolerance may be distinguished, namely lactase deficiency in premature infants, congenital lactase deficiency, adult-type hypolactasia and secondary lactase intolerance. An overview of the main uses of lactose in human nutrition and in the pharmaceutical industry and the problems derived from this circumstance are described in this review.
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Affiliation(s)
- Rafael G Seoane
- Area of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
| | - Verónica Garcia-Recio
- Area of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
| | - Manuel Garrosa
- Area of Histology, Faculty of Medicine and INCYL, University of Valladolid, 47005 Valladolid, Spain
| | - María Á Rojo
- Area of Experimental Sciences, Miguel de Cervantes European University, 47012 Valladolid, Spain
| | - Pilar Jiménez
- Area of Nutrition and Food Sciences, Faculty of Medicine, University of Valladolid, 47005 Valladolid, Spain
| | - Tomás Girbés
- Area of Nutrition and Food Sciences, Faculty of Medicine, University of Valladolid, 47005 Valladolid, Spain
| | - Manuel Cordoba-Diaz
- Area of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain.,University Institute of Industrial Pharmacy (IUFI), Complutense University of Madrid, 28040 Madrid, Spain
| | - Damián Cordoba-Diaz
- Area of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain.,University Institute of Industrial Pharmacy (IUFI), Complutense University of Madrid, 28040 Madrid, Spain
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Couce ML, Sánchez-Pintos P, González-Vioque E, Leis R. Clinical Utility of LCT Genotyping in Children with Suspected Functional Gastrointestinal Disorder. Nutrients 2020; 12:nu12103017. [PMID: 33019743 PMCID: PMC7601291 DOI: 10.3390/nu12103017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 09/28/2020] [Accepted: 09/28/2020] [Indexed: 12/16/2022] Open
Abstract
Genetic testing is a good predictor of lactase persistence (LP) in specific populations but its clinical utility in children is less clear. We assessed the role of lactose malabsorption in functional gastrointestinal disorders (FGID) in children and the correlation between the lactase non-persistence (LNP) genotype and phenotype, based on exhaled hydrogen and gastrointestinal symptoms, during a hydrogen breath test (HBT). We also evaluate dairy consumption in this sample. We conducted a 10-year cross-sectional study in a cohort of 493 children with suspected FGID defined by Roma IV criteria. Distribution of the C/T-13910 genotype was as follows: CC, 46.0%; TT, 14.4% (LP allele frequency, 34.1%). The phenotype frequencies of lactose malabsorption and intolerance were 36.3% and 41.5%, respectively. We observed a strong correlation between genotype and both lactose malabsorption (Cramér’s V, 0.28) and intolerance (Cramér’s V, 0.54). The frequency of the LNP genotype (p = 0.002) and of malabsorption and intolerance increased with age (p = 0.001 and 0.002, respectively). In 61% of children, evaluated dairy consumption was less than recommended. No association was observed between dairy intake and diagnosis. In conclusion, we found a significant correlation between genotype and phenotype, greater in older children, suggesting that the clinical value of genetic testing increases with age.
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Affiliation(s)
- María L. Couce
- Department of Pediatrics, University Clinical Hospital of Santiago de Compostela, IDIS-Health Research Institute of Santiago de Compostela, 15704 Santiago de Compostela, Spain; (E.G.-V.); (R.L.)
- CIBERER, Instituto Salud Carlos III, 28029 Madrid, Spain
- Department of Pediatrics, Universidad de Santiago de Compostela, 15704 Santiago de Compostela, Spain
- Correspondence: (M.L.C.); (P.S.-P.); Tel.: +34-981950151 (M.L.C.); +34-981950134 (P.S.-P.)
| | - Paula Sánchez-Pintos
- Department of Pediatrics, University Clinical Hospital of Santiago de Compostela, IDIS-Health Research Institute of Santiago de Compostela, 15704 Santiago de Compostela, Spain; (E.G.-V.); (R.L.)
- CIBERER, Instituto Salud Carlos III, 28029 Madrid, Spain
- Department of Pediatrics, Universidad de Santiago de Compostela, 15704 Santiago de Compostela, Spain
- Correspondence: (M.L.C.); (P.S.-P.); Tel.: +34-981950151 (M.L.C.); +34-981950134 (P.S.-P.)
| | - Emiliano González-Vioque
- Department of Pediatrics, University Clinical Hospital of Santiago de Compostela, IDIS-Health Research Institute of Santiago de Compostela, 15704 Santiago de Compostela, Spain; (E.G.-V.); (R.L.)
- CIBERER, Instituto Salud Carlos III, 28029 Madrid, Spain
| | - Rosaura Leis
- Department of Pediatrics, University Clinical Hospital of Santiago de Compostela, IDIS-Health Research Institute of Santiago de Compostela, 15704 Santiago de Compostela, Spain; (E.G.-V.); (R.L.)
- Department of Pediatrics, Universidad de Santiago de Compostela, 15704 Santiago de Compostela, Spain
- CIBEROBN, Instituto Salud Carlos III, 28029 Madrid, Spain
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Shrestha A, Barnett MPG, Perry JK, Cameron-Smith D, Milan AM. Evaluation of breath, plasma, and urinary markers of lactose malabsorption to diagnose lactase non-persistence following lactose or milk ingestion. BMC Gastroenterol 2020; 20:204. [PMID: 32600320 PMCID: PMC7325051 DOI: 10.1186/s12876-020-01352-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 06/17/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Adult lactase non-persistence (LNP) is due to low lactase expression, resulting in lactose malabsorption (LM). LNP is a genetic trait, but is typically determined by LM markers including breath H2, blood glucose, and urinary galactose after a lactose tolerance test. Known validity of these markers using milk is limited, despite being common practice. Compositional variation, such as β-casein variants, in milk may impact diagnostic efficacy. This study aimed to evaluate the diagnostic accuracy to detect LNP using these commonly measured LM markers after both lactose and milk challenges. METHODS Fourty healthy young women were challenged with 50 g lactose then randomized for separate cross-over visits to ingest 750 mL milk (37.5 g lactose) as conventional (both A1 and A2 β-casein) and A1 β-casein-free (a2 Milk™) milk. Blood, breath and urine were collected prior to and up to 3 h following each challenge. The presence of C/T13910 and G/A22018 polymorphisms, determined by restriction fragment length polymorphism, was used as the diagnostic reference for LNP. RESULTS Genetic testing identified 14 out of 40 subjects as having LNP (C/C13910 and G/G22018). All three LM markers (breath H2, plasma glucose and urinary galactose/creatinine) discriminated between lactase persistence (LP) and LNP following lactose challenge with an area under the receiver operating characteristic (ROC) curve (AUC) of 1.00, 0.75 and 0.73, respectively. Plasma glucose and urinary galactose/creatinine were unreliable (AUC < 0.70) after milk ingestion. The specificity of breath H2 remained high (100%) when milk was used, but sensitivity was reduced with conventional (92.9%) and a2 Milk™ (78.6%) compared to lactose (sensitivities adjusted for lactose content). The breath H2 optimal cut-off value was lower with a2 Milk™ (13 ppm) than conventional milk (21 ppm). Using existing literature cut-off values the sensitivity and specificity of breath H2 was greater than plasma glucose to detect LNP following lactose challenge whereas values obtained for urinary galactose/creatinine were lower than the existing literature cut-offs. CONCLUSION This study showed accurate diagnosis of LNP by breath H2 irrespective of the substrate used, although the diagnostic threshold may vary depending on the lactose substrate or the composition of the milk. TRIAL REGISTRATION ACTRN12616001694404 . Registered prospectively on December 9, 2016.
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Affiliation(s)
- Aahana Shrestha
- The Liggins Institute, The University of Auckland, Auckland, New Zealand
- The Riddet Institute, Palmerston North, New Zealand
| | - Matthew P G Barnett
- The Riddet Institute, Palmerston North, New Zealand
- Food Nutrition & Health Team, AgResearch Limited, Palmerston North, New Zealand
- The High-Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Jo K Perry
- The Liggins Institute, The University of Auckland, Auckland, New Zealand
| | - David Cameron-Smith
- The Liggins Institute, The University of Auckland, Auckland, New Zealand
- The Riddet Institute, Palmerston North, New Zealand
- Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore, Singapore
| | - Amber M Milan
- The Liggins Institute, The University of Auckland, Auckland, New Zealand.
- Food Nutrition & Health Team, AgResearch Limited, Palmerston North, New Zealand.
- The High-Value Nutrition National Science Challenge, Auckland, New Zealand.
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Araujo EM, Dos Santos L, Coutinho R, Assis V, Brandão N, Almeida D, Conceição G, Figueredo C, Fonseca H, Lima MDL, Lemaire D, Rios D. Genetic and Oral Tests for the Diagnosis of Lactose Intolerance in Mixed-Ancestry Brazilians with Metabolic Syndrome. Lifestyle Genom 2019; 12:1-9. [PMID: 31352438 DOI: 10.1159/000501690] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Accepted: 06/21/2019] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/AIMS Metabolic syndrome (MetS) comprises a cluster of physiological and anthropometric abnormalities. MetS has been linked to lactose intolerance (LI). The aim of this study was to compare the sensitivity and specificity to detect LI using 2 different tests: (1) a genetic test and (2) an oral lactose tolerance test (OLTT). METHODS Two hundred and fifty-four MetS patients, ≥20 years of age, of both genders, were recruited for this comparative study. Nine single nucleotide polymorphisms (SNPs) were selected for genetic investigation: rs182549and rs4988235(both considered "gold standard"); rs56064699; rs148142676; rs562211644; rs59533246; rs3754689; rs2278544,and rs10552864(as potential novel SNPs). Sensitivity and specificity, as well as positive and negative predictive values, were calculated for each genotype using WINPEPI version 11.65. Differences between positive and negative OLTT groups were considered statistically significant when p ≤ 0.05. RESULTS Among the selected SNPs, only rs182549(p < 0.001) and rs4988235(p < 0.001) gave similar results compared to an OLTT. The sensitivity of both SNPs to detect LI was 87 and 86%, and specificity was 83 and 82.5%, respectively. CONCLUSION Genetic tests using rs182549and rs4988235SNPs showed high agreement with OLTT. These genetic tests may be a good option to replace OLTT in MetS patients.
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Affiliation(s)
- Edilene Maria Araujo
- Nucleus of Research and Extension in Nutritional Genomics and Metabolic Dysfunctions (GENUT), Life Sciences Department (DCV), University of the State of Bahia (UNEB), Salvador, Brazil, .,Posgraduate Program in Biotechnology (PPGBiotec), State University of Feira de Santana (UEFS), Salvador, Brazil, .,Interactive Process of Organs and Systems (PPGorgsystem), Health Sciences Institute, Federal University of Bahia, Salvador, Brazil,
| | - Luama Dos Santos
- Nucleus of Research and Extension in Nutritional Genomics and Metabolic Dysfunctions (GENUT), Life Sciences Department (DCV), University of the State of Bahia (UNEB), Salvador, Brazil.,Interactive Process of Organs and Systems (PPGorgsystem), Health Sciences Institute, Federal University of Bahia, Salvador, Brazil
| | - Radamés Coutinho
- Nucleus of Research and Extension in Nutritional Genomics and Metabolic Dysfunctions (GENUT), Life Sciences Department (DCV), University of the State of Bahia (UNEB), Salvador, Brazil.,Interactive Process of Organs and Systems (PPGorgsystem), Health Sciences Institute, Federal University of Bahia, Salvador, Brazil
| | - Viviane Assis
- Nucleus of Research and Extension in Nutritional Genomics and Metabolic Dysfunctions (GENUT), Life Sciences Department (DCV), University of the State of Bahia (UNEB), Salvador, Brazil
| | - Najara Brandão
- Nucleus of Research and Extension in Nutritional Genomics and Metabolic Dysfunctions (GENUT), Life Sciences Department (DCV), University of the State of Bahia (UNEB), Salvador, Brazil
| | - Daniela Almeida
- Nucleus of Research and Extension in Nutritional Genomics and Metabolic Dysfunctions (GENUT), Life Sciences Department (DCV), University of the State of Bahia (UNEB), Salvador, Brazil.,Interactive Process of Organs and Systems (PPGorgsystem), Health Sciences Institute, Federal University of Bahia, Salvador, Brazil
| | - Gildásio Conceição
- Association of Parents and Friends of the Exceptional (APAE), Biochemical Analysis Laboratory, Salvador, Brazil
| | - Camila Figueredo
- Department of Biointeractive Science, Federal University of Bahia, Salvador, Brazil
| | - Hellen Fonseca
- Department of Biointeractive Science, Federal University of Bahia, Salvador, Brazil
| | - Maria de Lourdes Lima
- Bahia School of Medicine and Public Health (EBMSP), University Salvador (UNIFACS), Salvador, Brazil
| | - Denise Lemaire
- Nucleus of Research and Extension in Nutritional Genomics and Metabolic Dysfunctions (GENUT), Life Sciences Department (DCV), University of the State of Bahia (UNEB), Salvador, Brazil.,Interactive Process of Organs and Systems (PPGorgsystem), Health Sciences Institute, Federal University of Bahia, Salvador, Brazil
| | - Domingos Rios
- Nucleus of Research and Extension in Nutritional Genomics and Metabolic Dysfunctions (GENUT), Life Sciences Department (DCV), University of the State of Bahia (UNEB), Salvador, Brazil.,Posgraduate Program in Biotechnology (PPGBiotec), State University of Feira de Santana (UEFS), Salvador, Brazil
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10
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Congruency of Genetic Predisposition to Lactase Persistence and Lactose Breath Test. Nutrients 2019; 11:nu11061383. [PMID: 31226742 PMCID: PMC6628305 DOI: 10.3390/nu11061383] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Revised: 06/13/2019] [Accepted: 06/18/2019] [Indexed: 12/16/2022] Open
Abstract
The physiological decline of lactase production in adulthood, in some individuals, is responsible for the so-called “Lactose Intolerance.” This clinical syndrome presents with gastrointestinal and non-gastrointestinal symptoms following the consumption of dairy containing food. Lactose intolerance can be evaluated by means of the Lactose Breath Test (phenotype) and/or genetic evaluation of lactase-gene polymorphism (genotype). A comparison of the two tests was carried out in a large number of symptomatic adult subjects, which are selected and not representative of the general population. Congruency was as high as 88.6%. Among lactase non-persistent (genotype C/C), 14 subjects showed a negative Lactose Breath Test (LBT), possibly due to young age. Among lactase-persistent (genotype C/T), four subjects showed a positive LBT, which helps to diagnose secondary lactose intolerance. Symptoms, both gastrointestinal and extra-gastrointestinal, were reported by 90% of patients during the breath test. Clinical use of both tests in the same patients could be taken into consideration as a sharp diagnostic tool. We suggest considering the use of the genetic test after LBT administration, when secondary hypolactasia is suspected, for completion of diagnostic procedures.
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11
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Real-time PCR based detection of the lactase non-persistence associated genetic variant LCT-13910C>T directly from whole blood. Mol Biol Rep 2019; 46:2379-2385. [PMID: 30790118 DOI: 10.1007/s11033-019-04696-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Accepted: 02/09/2019] [Indexed: 01/20/2023]
Abstract
Primary hypolactasia is the main cause of lactose intolerance in adults. It is strongly associated with the single genetic variant LCT-13910C>T, located upstream of the lactase encoding gene. Consequently, analysis of LCT-13910C>T has been recommended as a direct genetic test for the trait. The aim of our study was to develop a TaqMan probe based real-time PCR protocol for the detection of the LCT-13910C>T variant directly from whole blood, circumventing DNA isolation. The LCT-13910C>T variant was determined using the DirectBlood Genotyping PCR Kit (myPOLS Biotec, Konstanz, Germany) together with an in-house TaqMan primer-probe assay. Validity and specificity of the assay was evaluated using EDTA anti-coagulated whole blood samples and corresponding DNA samples. Results from real-time PCR were compared with results obtained by Sanger sequencing from 105 blinded whole blood samples. Validity and specificity of the assay using whole blood were comparable to those using purified genomic DNA as substrate in PCR. Genetic analysis of blood samples were in complete agreement with results obtained by Sanger sequencing. In conclusion, we present a reliable real-time PCR protocol for the detection of the LCT-13910C>T variant directly from whole blood further facilitating diagnosis of primary hypolactasia in symptomatic patients.
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12
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Lactose Maldigestion, Malabsorption, and Intolerance: A Comprehensive Review with a Focus on Current Management and Future Perspectives. Nutrients 2018; 10:nu10111599. [PMID: 30388735 PMCID: PMC6265758 DOI: 10.3390/nu10111599] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Revised: 10/19/2018] [Accepted: 10/23/2018] [Indexed: 12/12/2022] Open
Abstract
Milk is a fundamental component of the diet of every mammal; nevertheless, not every individual can tolerate this kind of food, especially in adulthood. However, lactose intolerance has only been recognized in the last 50 years, and currently, lactose intolerance is defined as a clinical syndrome characterized by pain, abdominal distention, flatulence, and diarrhoea that occur after lactose consumption. Lactose is currently a common disaccharide in human nutrition, both in breastfed infants and in adults, but its digestion requires a specialized enzyme called lactase. The genetically programmed reduction in lactase activity during adulthood affects most of the world’s adult population and can cause troublesome digestive symptoms, which may also vary depending on the amount of residual lactase activity; the small bowel transit time; and, especially, the amount of ingested lactose. Several diagnostic tests are currently available for lactose intolerance, but the diagnosis remains challenging. The treatment for lactose intolerance mainly consists of reducing or eliminating the dietetic amount of lactose until the symptoms disappear, but this is hard to achieve, as lactose is present in dairy products and is even commonly used as a food additive. In addition to dietetic restriction of lactose-containing foods, lactase can be administered as an enzymatic food supplement, but its efficacy is still controversial. Recently, probiotics have been proposed for the management of lactose intolerance; certain probiotic strains have shown specific β-galactosidase activity, thus aiding in the digestion of lactose. The aim of this paper was to review the current knowledge about lactose intolerance and to discuss the potential for the use of specific probiotic strains such as dietary supplements in lactose-intolerant patients.
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13
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Wortmann AC, Simon D, Mazzoleni LE, Sander GB, Francesconi CFDM, Nabinger DD, Grott CS, Rech TF, Mazzoleni F, Lunge VR, Bona LRD, Milbradt TC, Silveira TRD. The association between adult-type hypolactasia and symptoms of functional dyspepsia. Genet Mol Biol 2018; 41:92-97. [PMID: 29384557 PMCID: PMC5901505 DOI: 10.1590/1678-4685-gmb-2017-0015] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Accepted: 08/20/2017] [Indexed: 12/15/2022] Open
Abstract
Functional dyspepsia and lactose intolerance (adult-type hypolactasia, ATH) are
common conditions that may coexist or even be confounded. Their clinical
presentation can be similar, however, lactose intolerance does not form part of
the diagnostic investigation of functional dyspepsia. Studies on the association
between functional dyspepsia and ATH are scarce. This study aimed to evaluate
whether ATH is associated with symptoms of functional dyspepsia. Patients
fulfilling the Rome III diagnostic criteria for functional dyspepsia underwent
genetic testing for ATH. Dyspeptic symptoms were evaluated and scored according
to a validated questionnaire. The diagnostic criteria for ATH was a CC genotype
for the -13910C/T polymorphism, located upstream of the lactase gene. The mean
scores for dyspeptic symptoms were compared between patients with ATH and those
with lactase persistence. A total of 197 functional dyspeptic patients were
included in the study. Mean age was 47.7 years and 82.7% patients were women.
Eighty-eight patients (44.7%) had a diagnosis of ATH. Abdominal bloating scores
were higher in ATH patients compared to the lactase persistent patients
(P=0.014). The remaining dyspeptic symptom scores were not
significantly different between the two groups. The study results demonstrate an
association between ATH and bloating in patients with functional dyspepsia.
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Affiliation(s)
- André Castagna Wortmann
- Postgraduate Program in Sciences of Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Daniel Simon
- Human Molecular Genetics Laboratory, Universidade Luterana do Brasil (ULBRA), Canoas, RS, Brazil
| | - Luiz Edmundo Mazzoleni
- Postgraduate Program in Sciences of Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.,Division of Gastroenterology, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil
| | - Guilherme Becker Sander
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil
| | - Carlos Fernando de Magalhães Francesconi
- Postgraduate Program in Sciences of Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.,Division of Gastroenterology, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil
| | - Débora Dreher Nabinger
- Human Molecular Genetics Laboratory, Universidade Luterana do Brasil (ULBRA), Canoas, RS, Brazil
| | - Camila Schultz Grott
- Human Molecular Genetics Laboratory, Universidade Luterana do Brasil (ULBRA), Canoas, RS, Brazil
| | - Tássia Flores Rech
- Human Molecular Genetics Laboratory, Universidade Luterana do Brasil (ULBRA), Canoas, RS, Brazil
| | - Felipe Mazzoleni
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil
| | - Vagner Ricardo Lunge
- Molecular Diagnostic Laboratory, Universidade Luterana do Brasil (ULBRA), Canoas, RS, Brazil
| | - Laura Renata de Bona
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil
| | - Tobias Cancian Milbradt
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil
| | - Themis Reverbel da Silveira
- Postgraduate Program in Sciences of Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
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14
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Cozma-Petruţ A, Loghin F, Miere D, Dumitraşcu DL. Diet in irritable bowel syndrome: What to recommend, not what to forbid to patients! World J Gastroenterol 2017; 23:3771-3783. [PMID: 28638217 PMCID: PMC5467063 DOI: 10.3748/wjg.v23.i21.3771] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Revised: 04/08/2017] [Accepted: 05/04/2017] [Indexed: 02/06/2023] Open
Abstract
A substantial proportion of patients with irritable bowel syndrome (IBS) associate their symptoms with the ingestion of specific foods. Therefore, in recent years, scientific research has increasingly focused on the role of diet in IBS and dietary management is now considered an important tool in IBS treatment. This article reviews the main dietary approaches in IBS emphasizing evidence from experimental and observational studies and summarizing the main diet and lifestyle recommendations provided by dietary guidelines and scientific literature. Despite the limited evidence for a beneficial role, general advice on healthy eating and lifestyle is recommended as the first-line approach in the dietary management of IBS. Standard recommendations include adhering to a regular meal pattern, reducing intake of insoluble fibers, alcohol, caffeine, spicy foods, and fat, as well as performing regular physical activity and ensuring a good hydration. Second-line dietary approach should be considered where IBS symptoms persist and recommendations include following a low FODMAP diet, to be delivered only by a healthcare professional with expertise in dietary management. The efficacy of this diet is supported by a growing body of evidence. In contrast, the role of lactose or gluten dietary restriction in the treatment of IBS remains subject to ongoing research with a lack of high-quality evidence. Likewise, further clinical trials are needed to conclude the efficacy of probiotics on IBS symptoms.
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15
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Domínguez-Jiménez JL, Fernández-Suárez A. Diagnóstico de la intolerancia a la lactosa. Med Clin (Barc) 2017; 148:262-264. [DOI: 10.1016/j.medcli.2016.11.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Accepted: 11/20/2016] [Indexed: 11/28/2022]
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16
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Fernández-Bañares F, Accarino A, Balboa A, Domènech E, Esteve M, Garcia-Planella E, Guardiola J, Molero X, Rodríguez-Luna A, Ruiz-Cerulla A, Santos J, Vaquero E. Diarrea crónica: definición, clasificación y diagnóstico. GASTROENTEROLOGIA Y HEPATOLOGIA 2016; 39:535-59. [DOI: 10.1016/j.gastrohep.2015.09.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Revised: 09/21/2015] [Accepted: 09/30/2015] [Indexed: 12/16/2022]
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17
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Enko D, Kriegshäuser G, Halwachs-Baumann G, Mangge H, Schnedl WJ. Serum diamine oxidase activity is associated with lactose malabsorption phenotypic variation. Clin Biochem 2016; 50:50-53. [PMID: 27593109 DOI: 10.1016/j.clinbiochem.2016.08.019] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Revised: 08/30/2016] [Accepted: 08/31/2016] [Indexed: 10/21/2022]
Abstract
OBJECTIVES Recently, an intermediate lactose intolerance (LI) phenotype based on the lactase gene (LCT) C/T-13910 polymorphism was proposed. However, a multifactorial genesis of LI phenotypic variation including endogenous and exogenous factors cannot be ruled out. Therefore, this study was conducted to investigate a possible association between serum diamine oxidase (DAO) and LI phenotypes in individuals with lactose malabsorption (LM). DESIGN AND METHODS A total of 121 ambulatory patients with LM were included in this retrospective study. The lactose hydrogen breath test (LHBT) and serum DAO activity measurements were performed on the same day. A thorough anamnesis with respect to gastrointestinal symptoms was carried out at the initial consultation. RESULTS In total, 44 (36.4%) patients with a serum DAO activity <10U/mL showed higher H2 levels after 60 (mean: 53.7±57.6 vs 34.5±31.7 parts per million [ppm], p=0.116), 90 (mean: 70.3±57.5 vs 52.7±41.4ppm, p=0.184) and 120min (mean: 98.9±72.5 vs 67.9±44.9ppm, p=0.012) during LHBT compared to 77 (63.6%) patients with a serum DAO activity ≥10U/mL. Individuals with a serum DAO activity <10U/mL tended to report gastrointestinal symptoms during the LHBT more often (p=0.091). CONCLUSIONS Our findings suggest that patients with LM and a serum DAO activity level<10U/mL had higher end-expiratory H2 levels and tended to be more symptomatic during the LHBT compared to LM patients with DAO activity levels ≥10U/mL.
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Affiliation(s)
- Dietmar Enko
- Institute of Clinical Chemistry and Laboratory Medicine, General Hospital Steyr, Sierningerstraße 170, 4400 Steyr, Austria; Clinical Institute of Medical and Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
| | - Gernot Kriegshäuser
- Institute of Clinical Chemistry and Laboratory Medicine, General Hospital Steyr, Sierningerstraße 170, 4400 Steyr, Austria; Clinical Institute of Medical and Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
| | - Gabriele Halwachs-Baumann
- Institute of Clinical Chemistry and Laboratory Medicine, General Hospital Steyr, Sierningerstraße 170, 4400 Steyr, Austria.
| | - Harald Mangge
- Clinical Institute of Medical and Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
| | - Wolfgang J Schnedl
- Practice for General Internal Medicine, Dr. Theodor-Körner-Straße 19b, 8600 Bruck an der Mur, Austria.
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18
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Abstract
Despite being one of the most common conditions leading to gastroenterological referral, irritable bowel syndrome (IBS) is poorly understood. However, recent years have seen major advances. These include new understanding of the role of both inflammation and altered microbiota as well as the impact of dietary intolerances as illuminated by magnetic resonance imaging (MRI), which has thrown new light on IBS. This article will review new data on how excessive bile acid secretion mediates diarrhea and evidence from post infectious IBS which has shown how gut inflammation can alter gut microbiota and function. Studies of patients with inflammatory bowel disease (IBD) have also shown that even when inflammation is in remission, the altered enteric nerves and abnormal microbiota can generate IBS-like symptoms. The efficacy of the low FODMAP diet as a treatment for bloating, flatulence, and abdominal discomfort has been demonstrated by randomized controlled trials. MRI studies, which can quantify intestinal volumes, have provided new insights into how FODMAPs cause symptoms. This article will focus on these areas together with recent trials of new agents, which this author believes will alter clinical practice within the foreseeable future.
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Affiliation(s)
- Robin Spiller
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
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19
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Domínguez Jiménez JL, Fernández Suárez A, Muñoz Colmenero AÚ, Fatela Cantillo D, López Pelayo I. Primary hypolactasia diagnosis: Comparison between the gaxilose test, shortened lactose tolerance test, and clinical parameters corresponding to the C/T-13910 polymorphism. Clin Nutr 2016; 36:471-476. [PMID: 26847948 DOI: 10.1016/j.clnu.2016.01.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2015] [Revised: 12/13/2015] [Accepted: 01/11/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS There is no consensus on the most accurate method to diagnose primary hypolactasia. We aimed to compare the diagnostic accuracy of the new gaxilose test with 2 traditional tests (lactose tolerance test and clinical criteria) for the diagnosis of primary hypolactasia using the C/T-13910 polymorphism as a reference standard. METHODS Patients with a clinical suspicion of lactose intolerance were subjected to gaxilose tests, shortened lactose tolerance tests, and symptom questionnaires before and after overload with 50 g lactose and after a lactose-free diet. The diagnostic accuracy and degree of agreement and correlation were assessed using a genetic test (C/T-13910 polymorphism) as a reference standard and their respective 95% confidence intervals. RESULTS Thirty consecutive patients (70% women) participated in the study. The genetic test confirmed the C/T-13910 polymorphism in 11 patients (36.8%). The presence of diarrhoea and the symptom score after lactose overload, along with the tolerance test, were the variables with the highest degree of agreement (κ > 0.60). Area under the ROC curve was >0.82 (p < 0.05), with sensitivity and specificity values of >0.80. However, the gaxilose test obtained lower values: κ, 0.47; area under curve, 0.75 (0.57-0.94); sensitivity, 0.82 (0.55-1); and specificity, 0.68 (0.45-0.92). The multivariate analysis showed an association between the post-overload symptom questionnaire and the results of the genetic test (odds ratio: 1.17; 1.04-1.31; p < 0.01). CONCLUSIONS The presence of diarrhoea and the symptom score after overload with 50 g lactose showed a higher degree of agreement and diagnostic accuracy for primary hypolactasia than the gaxilose test when the genetic test is used as a reference standard.
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Affiliation(s)
- José Luis Domínguez Jiménez
- Department of Gastroenterology and Hepatology, Alto Guadalquivir Healthcare Agency, Alto Guadalquivir Hospital, Andújar, Jaén, Spain.
| | - Antonio Fernández Suárez
- Department of Biotechnology, Alto Guadalquivir Healthcare Agency, Alto Guadalquivir Hospital, Andújar, Jaén, Spain
| | | | - Daniel Fatela Cantillo
- Department of Biotechnology, Alto Guadalquivir Healthcare Agency, Alto Guadalquivir Hospital, Andújar, Jaén, Spain
| | - Iratxe López Pelayo
- Department of Biotechnology, U.G.C. Laboratory, Puerta del Mar Hospital, Cádiz, Spain
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20
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Zheng X, Chu H, Cong Y, Deng Y, Long Y, Zhu Y, Pohl D, Fried M, Dai N, Fox M. Self-reported lactose intolerance in clinic patients with functional gastrointestinal symptoms: prevalence, risk factors, and impact on food choices. Neurogastroenterol Motil 2015; 27:1138-46. [PMID: 26095206 DOI: 10.1111/nmo.12602] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2014] [Accepted: 04/27/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND Many patients complain of abdominal symptoms with dairy products; however, clinical and psychosocial factors associated with self-reported lactose intolerance (SLI) have not been assessed in large studies. In particular, data are lacking from lactase deficient populations. This prospective cohort study assessed the prevalence of, and risk factors for, SLI in Chinese patients attending a gastroenterology clinic. METHODS Consecutive patients completed questionnaires to assess digestive health (Rome III), psychological state (HADS), life event stress (LES), food intake, and quality-of-life (SF-8). A representative sample completed genetic studies and hydrogen breath testing (HBT) at the clinically relevant dose of 20 g lactose. KEY RESULTS SLI was present in 411/910 (45%) clinic patients with functional abdominal symptoms. The genotype in all subjects was C/C-13910. A small number of novel SNPs in lactase promoter region were identified, including C/T-13908 which appeared to confer lactase persistence. Over half of the patients (54%) completed the 20 g lactose HBT with 58% (285/492) reporting typical symptoms. Positive and negative predictive values of SLI for abdominal symptoms during HBT were 60% and 44%, respectively. Psychological state and stress were not associated with SLI in clinic patients. SLI impacted on physical quality-of-life and was associated with reduced ingestion of dairy products, legumes, and dried fruit (p ≤ 0.05). CONCLUSIONS & INFERENCES In a lactase deficient population, approximately half of patients attending clinic with functional gastrointestinal symptoms reported intolerance to dairy products; however, SLI did not predict findings on 20 g lactose HBT. Independent of psychosocial factors, SLI impacted on quality-of-life and impacted on food choices with restrictions not limited to dairy products.
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Affiliation(s)
- X Zheng
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - H Chu
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Y Cong
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Y Deng
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Y Long
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Y Zhu
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - D Pohl
- Division of Gastroenterology & Hepatology, University Hospital Zürich, Zürich, Switzerland.,Zürich Centre for Integrative Human Physiology (ZIHP), University of Zürich, Zürich, Switzerland
| | - M Fried
- Division of Gastroenterology & Hepatology, University Hospital Zürich, Zürich, Switzerland.,Zürich Centre for Integrative Human Physiology (ZIHP), University of Zürich, Zürich, Switzerland
| | - N Dai
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - M Fox
- Division of Gastroenterology & Hepatology, University Hospital Zürich, Zürich, Switzerland.,Zürich Centre for Integrative Human Physiology (ZIHP), University of Zürich, Zürich, Switzerland
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21
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Yang JF, Fox M, Chu H, Zheng X, Long YQ, Pohl D, Fried M, Dai N. Four-sample lactose hydrogen breath test for diagnosis of lactose malabsorption in irritable bowel syndrome patients with diarrhea. World J Gastroenterol 2015; 21:7563-7570. [PMID: 26140004 PMCID: PMC4481453 DOI: 10.3748/wjg.v21.i24.7563] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Revised: 02/20/2015] [Accepted: 03/31/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To validate 4-sample lactose hydrogen breath testing (4SLHBT) compared to standard 13-sample LHBT in the clinical setting.
METHODS: Irritable bowel syndrome patients with diarrhea (IBS-D) and healthy volunteers (HVs) were enrolled and received a 10 g, 20 g, or 40 g dose lactose hydrogen breath test (LHBT) in a randomized, double-blinded, controlled trial. The lactase gene promoter region was sequenced. Breath samples and symptoms were acquired at baseline and every 15 min for 3 h (13 measurements). The detection rates of lactose malabsorption (LM) and lactose intolerance (LI) for a 4SLHBT that acquired four measurements at 0, 90, 120, and 180 min from the same data set were compared with the results of standard LHBT.
RESULTS: Sixty IBS-D patients and 60 HVs were studied. The genotype in all participants was C/C-13910. LM and LI detection rates increased with lactose dose from 10 g, 20 g to 40 g in both groups (P < 0.001). 4SLHBT showed excellent diagnostic concordance with standard LHBT (97%-100%, Kappa 0.815-0.942) with high sensitivity (90%-100%) and specificity (100%) at all three lactose doses in both groups.
CONCLUSION: Reducing the number of measurements from 13 to 4 samples did not significantly impact on the accuracy of LHBT in health and IBS-D. 4SLHBT is a valid test for assessment of LM and LI in clinical practice.
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Sun J, Lin J, Parashette K, Zhang J, Fan R. Association of lymphocytic colitis and lactase deficiency in pediatric population. Pathol Res Pract 2014; 211:138-44. [PMID: 25523228 DOI: 10.1016/j.prp.2014.11.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2014] [Revised: 10/08/2014] [Accepted: 11/11/2014] [Indexed: 01/29/2023]
Abstract
Characterized by colonic mucosa intraepithelial lymphocytosis, lymphocytic colitis is primarily an entity presented in the middle-aged to elderly patient population. Very few large series of lymphocytic colitis of childhood occurrence are available in the medical literature. Ten cases each of lymphocytic colitis and of colonic lymphocytosis of other diagnosis, all with duodenal disaccharidases analysis data, were collected from the files of our institution. The electronic medical records were reviewed and multiple variables were analyzed. The ten patients with lymphocytic colitis presented with diarrhea. Of these, three had abdominal pain. The age range was 2-18 years. Nearly all patients were Caucasian (90%) and 70% were female. Endoscopically, most had normal appearing colonic mucosa. Significant past medical history, family medical history and associated comorbidities included celiac disease, Down syndrome, juvenile arthritis and other autoimmune diseases. Interestingly, the most revealing observation was that the majority of cases (80%) were associated with lactase deficiency and, for the most part, gastrointestinal symptoms improved simply by treatment with Lactaid or avoidance of dairy products. This association is statistically significant. Our clinicopathological study indicates that the typical pediatric patient is a female Caucasian. A large of portion of the patients had associated lactase deficiency and improved on Lactaid supplement alone.
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Affiliation(s)
- Jihong Sun
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Riley Hospital for Children at IU Health, 702 Barnhill Drive, Indianapolis, IN 46202, USA
| | - Jingmei Lin
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Riley Hospital for Children at IU Health, 702 Barnhill Drive, Indianapolis, IN 46202, USA
| | - Kalayan Parashette
- Division of Pediatric Gastroenterology/Hepatology/Nutrition, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Jianjun Zhang
- Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA
| | - Rong Fan
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Riley Hospital for Children at IU Health, 702 Barnhill Drive, Indianapolis, IN 46202, USA.
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Santonocito C, Scapaticci M, Guarino D, Annicchiarico EB, Lisci R, Penitente R, Gasbarrini A, Zuppi C, Capoluongo E. Lactose intolerance genetic testing: is it useful as routine screening? Results on 1426 south-central Italy patients. Clin Chim Acta 2014; 439:14-7. [PMID: 25281930 DOI: 10.1016/j.cca.2014.09.026] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2014] [Revised: 09/09/2014] [Accepted: 09/24/2014] [Indexed: 12/15/2022]
Abstract
Adult-type hypolactasia is a widespread condition throughout the world, causing lactose malabsorption. Several studies suggested that the identification of C/T-13910 and G/A-22018 mutations, located upstream the gene encoding the lactase-phlorizin hydrolase (LPH), is a useful tool for the differential diagnosis of hypolactasia. We evaluated the frequencies of C/T-13910 and G/A-22018 variants in a central-south Italian population and the usefulness of lactase deficiency genetic testing in the clinic practice. The genomic DNA of 1426 patients and 1000 healthy controls from central-south Italy was isolated from peripheral whole blood and genotyped for the C/T-13910 and G/A-22018 polymorphisms by high-resolution melting analysis (HRMA) and sequencing. The frequencies of genotypes in the 1426 patients analysed were as follows: 1077 CC/GG (75.5%), 287 CT/GA (20.1%), 24 TT/AA (1.7%), 38 CC/GA (2.7%). Only 64 out of 1426 (4.5%) performed also L-BHT test, 29 of which were negative for L-BHT also in presence of different genotypes. Among the 35 individuals with L-BHT positive, 34 were CC/GG and only one CT/GA. Although lactose genetic test is a good predictor of persistence/non-persistence lactase in specific population, its use in the central-south Italy population should be limited given the high prevalence of the CCGG diplotype in normal individuals.
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Affiliation(s)
- Concetta Santonocito
- Laboratory of Clinical Molecular and Personalized Diagnostics, Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, Rome, Italy.
| | - Margherita Scapaticci
- Laboratory of Clinical Molecular and Personalized Diagnostics, Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, Rome, Italy
| | - Donatella Guarino
- Laboratory of Clinical Molecular and Personalized Diagnostics, Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, Rome, Italy
| | | | - Rosalia Lisci
- Laboratory of Clinical Molecular and Personalized Diagnostics, Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, Rome, Italy
| | - Romina Penitente
- Laboratory of Clinical Molecular and Personalized Diagnostics, Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, Rome, Italy
| | - Antonio Gasbarrini
- Department of Internal Medicine, Teaching Hospital "A. Gemelli," Catholic University of the Sacred Heart, Rome, Italy
| | - Cecilia Zuppi
- Laboratory of Clinical Molecular and Personalized Diagnostics, Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, Rome, Italy
| | - Ettore Capoluongo
- Laboratory of Clinical Molecular and Personalized Diagnostics, Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, Rome, Italy.
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Misselwitz B, Pohl D, Frühauf H, Fried M, Vavricka SR, Fox M. Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment. United European Gastroenterol J 2014; 1:151-9. [PMID: 24917953 DOI: 10.1177/2050640613484463] [Citation(s) in RCA: 114] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2012] [Accepted: 03/06/2013] [Indexed: 12/11/2022] Open
Abstract
Lactose malabsorption is a common condition caused by reduced expression or activity of lactase in the small intestine. In such patients, lactose intolerance is characterized by abdominal symptoms (e.g. nausea, bloating, and pain) after ingestion of dairy products. The genetic basis of lactose malabsorption is established and several tests for this condition are available, including genetic, endoscopic, and H2-breath tests. In contrast, lactose intolerance is less well understood. Recent studies show that the risk of symptoms after lactose ingestion depends on the dose of lactose, lactase expression, intestinal flora, and sensitivity of the gastrointestinal tract. Lactose intolerance has recently been defined as symptoms developing after ingestion of lactose which do not develop after placebo challenge in a person with lactose maldigestion. Such blinded testing might be especially important in those with functional gastrointestinal diseases in whom self-reported lactose intolerance is common. However, placebo-controlled testing is not part of current clinical practice. Updated protocols and high-quality outcome studies are needed. Treatment options of lactose intolerance include lactose-reduced diet and enzyme replacement. Documenting the response to multiple doses can guide rational dietary management; however, the clinical utility of this strategy has not been tested. This review summarizes the genetic basis, diagnosis, and treatment of lactose malabsorption and intolerance.
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Affiliation(s)
| | - Daniel Pohl
- University Hospital Zürich, Zürich, Switzerland
| | | | | | | | - Mark Fox
- Nottingham University Hospital, Nottingham, UK
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Abstract
The purpose of this literature review is to develop a thorough understanding of the research on food intolerance and its relationship to irritable bowel syndrome. Knowledge of the connection between the two conditions will assist allied healthcare professionals in working with patients to better manage their symptoms. Reduced healthcare costs may also result if patients are able to identify problematic foods and experience symptom improvement with diet changes. The review consists of an overview of food intolerance including prevalence, specific foods implicated including an in-depth review of research on bulk sweeteners, as well as methods of diagnosis. In addition, prevalence, specific foods associated with food intolerance in irritable bowel syndrome patients such as carbohydrates and lipids, nutritional consequences of food intolerance, and possible food-related methods of treatment including increased fiber intake are discussed. Finally, suggestions for future research and possible directions allied healthcare professionals can start with in assisting patients are provided.
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Lactose malabsorption testing in daily clinical practice: a critical retrospective analysis and comparison of the hydrogen/methane breath test and genetic test (c/t-13910 polymorphism) results. Gastroenterol Res Pract 2014; 2014:464382. [PMID: 24829570 PMCID: PMC4009220 DOI: 10.1155/2014/464382] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Accepted: 03/25/2014] [Indexed: 01/08/2023] Open
Abstract
The aim of this study was to establish a retrospective evaluation and comparison of the hydrogen/methane (H2/CH4) breath test and genetic test (C/T-13910 polymorphism) results in lactose malabsorption testing. In total 263 consecutive patients with suspected lactose malabsorption were included in this study. They underwent the H2/CH4 breath test following the ingestion of 50 g lactose and were tested for the C/T-13910 polymorphism. In total 51 patients (19.4%) had a C/C-13910 genotype, indicating primary lactose malabsorption. Only 19 patients (7.2%) also had a positive H2/CH4 breath test. All in all 136 patients (51.69%) had a C/T-13910 and 76 patients (28.91%) a T/T-13910 genotype, indicating lactase persistence. Four patients (1.5%) with the C/T-13910 genotype and one patient (0.4%) with the T/T-13910 genotype had a positive H2/CH4 breath test result, indicating secondary lactose malabsorption. Cohen's Kappa measuring agreement between the two methods was 0.44. Twenty patients (7.6%) with a positive H2/CH4 peak within 60 minutes after lactose ingestion were classified as patients with lactose-dependent small intestinal bacterial overgrowth (SIBO). In conclusion, only moderate agreement between the breath test and the genetic test was shown. Secondary lactose malabsorption as well as preanalytical limitations of the combined H2/CH4 breath test procedure can cause discrepant results. This trial is registered with K-42-13.
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27
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Al-Abri A, Bayoumi R. The Phenotype/Genotype Correlation of Lactase Persistence among Omani Adults. Oman Med J 2013; 28:341-4. [PMID: 24044061 DOI: 10.5001/omj.2013.98] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2013] [Accepted: 06/15/2013] [Indexed: 11/03/2022] Open
Abstract
OBJECTIVE To examine the correlation of lactase persistence phenotype with genotype in Omani adults. METHODS Lactase persistence phenotype was tested by hydrogen breath test in 52 Omani Adults using the Micro H2 analyzer. Results were checked against genotyping using direct DNA sequencing. RESULTS Forty one individuals with C/C-13910 and T/T-13915 genotypes had positive breath tests (≥20 ppm); while eight of nine individuals with T/C-13910 or T/G-13915 genotypes had negative breath tests (<20 ppm) and two subjects were non-hydrogen producers. The agreement between phenotype and genotype using Kappa value was very good (0.93). CONCLUSION Genotyping both T/C-13910 and T/G-13915 alleles can be used to assist diagnosis and predict lactose intolerance in the Omani population.
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Affiliation(s)
- Abdulrahim Al-Abri
- Department of Biochemistry, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box- 35, Postal Code 123, Muscat, Sultanate of Oman
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28
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Lamri A, Poli A, Emery N, Bellili N, Velho G, Lantieri O, Balkau B, Marre M, Fumeron F. The lactase persistence genotype is associated with body mass index and dairy consumption in the D.E.S.I.R. study. Metabolism 2013; 62:1323-9. [PMID: 23647908 DOI: 10.1016/j.metabol.2013.04.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2012] [Revised: 03/05/2013] [Accepted: 04/03/2013] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The T allele of a functional polymorphism (rs4988235: LCT-13910 C>T), close to the lactase gene, correlates with lactase persistence (LP) in adults. The LP genotype (TT+TC) has been associated with a higher BMI in European populations in cross-sectional studies. In the French D.E.S.I.R. cohort, a high consumption of dairy products was associated with a lower body weight gain over 9-years, and with a lower incidence of high plasma glucose levels and/or the metabolic syndrome. Our aim was to test in this study, the association of rs4988235 with BMI and related metabolic diseases, in interaction with dairy product consumption. METHODS Among 5212 subjects from D.E.S.I.R., 3575 Caucasians born in mainland France were genotyped and followed over 9years. RESULTS Those with the LP genotype (frequency: 78.5%) had a higher dairy product consumption, at inclusion and at year-9 (P<0.001). They also had a higher BMI at both time points (difference=0.3kg/m(2), P=0.05), but this effect was restricted to medium/high dairy product consumers (difference=0.5kg/m(2), P=0.006). This genotype was also associated with the metabolic syndrome (IDF definition), but this association disappeared after adjustment for BMI. In the whole population, the C allele was associated with a higher prevalence of impaired fasting glycemia and/or type 2 diabetes. CONCLUSIONS The lactase persistence genotype was shown to be associated with a higher BMI in a longitudinal study, mainly in those consuming high amounts of dairy products. The association of the C allele, responsible for lactase non-persistence, with the risk of hyperglycemia needs to be replicated.
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Affiliation(s)
- Amel Lamri
- INSERM, U695, Genetic Determinants of Type 2 Diabetes and Its Vascular Complications, Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, UMRS 695, UFR de Médecine Site Bichat, Paris, France
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29
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No association of LCT-13910 single nucleotide polymorphism with gastroenteritis in Korean children. Mol Cell Toxicol 2013. [DOI: 10.1007/s13273-013-0004-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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A comparison between lactose breath test and quick test on duodenal biopsies for diagnosing lactase deficiency in patients with self-reported lactose intolerance. J Clin Gastroenterol 2013; 47:148-52. [PMID: 22495813 DOI: 10.1097/mcg.0b013e31824e9132] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND A lactose breath test (LBT) is usually used to diagnose lactase deficiency, and a lactose quick test (LQT) has been proposed as a new test on duodenal biopsies to detect this disorder. GOALS We aimed to assess the diagnostic accuracy of LBT and LQT and their ability to predict the clinical response to a lactose-free diet in patients with self-reported lactose intolerance. STUDY Fifty-five patients (age 47 ± 14 y; M/F 15/36) underwent upper gastrointestinal endoscopy and 25g-LBT. Two duodenal biopsies were taken to determine lactase deficiency (normal, mild, or severe) by LQT and to rule out other causes of secondary lactose malabsorption. Patients with a positive LBT and normal LQT also underwent a glucose breath test to exclude small intestinal bacterial overgrowth as a cause of the former result. The severity of gastrointestinal symptoms was measured with a GSS questionnaire, under basal condition and 1 month after a lactose-free diet. RESULTS Lactose malabsorption was detected in 31/51 patients with LBT and in 37/51 patients with LQT (P = NS). Celiac disease was found in 2 patients. Two LBT+ patients showed a positive glucose breath test for small intestinal bacterial overgrowth. Eight patients had a mild hypolactasia by LQT and a negative LBT, but they had a significant improvement of symptoms after diet. LQT and LBT were concordant in 83% of cases and predicted the response to a lactose-free diet in 98% and 81% of the cases, respectively (P = 0.03). CONCLUSIONS LQT is as sensitive as LBT in detecting lactase deficiency; however, it seems to be more accurate than LBT in predicting the clinical response to a lactose-free diet.
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Manco L, Pires S, Lopes AI, Figueiredo I, Albuquerque D, Alvarez M, Rocha J, Abade A. Distribution of the - 13910C>T polymorphism in the general population of Portugal and in subjects with gastrointestinal complaints associated with milk consumption. Ann Hum Biol 2013; 40:205-8. [PMID: 23327608 DOI: 10.3109/03014460.2012.754943] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND The - 13910C>T polymorphism has been associated with lactase persistence (LP) in European populations. AIM To assess - 13910C>T genotypes across Portugal and in adult individuals with unspecific gastrointestinal complaints associated with milk consumption. SUBJECTS AND METHODS This study genotyped - 13910C>T in the general population from Northern (n = 64), Central (n = 70) and Southern (n = 65) Portugal and in 40 subjects with gastrointestinal symptoms. Additionally, the concordance was evaluated between breath-hydrogen test and - 13910C>T genotypes in 65 samples. RESULTS An overall frequency of 0.349 for the LP - 13910*T allele was estimated in the general population, with a noticeable decrease in the South (0.269) compared with North (0.383) and Centre (0.393). Among the symptomatic group, the frequency of the - 13910*T allele (0.363) was not significantly different from the general population. A 94% concordance was found between the breath-hydrogen and the molecular tests. CONCLUSIONS This study suggests that (i) the distribution of the LP polymorphism is not uniform across the country, (ii) genotyping - 13910C>T is a good diagnostic tool for lactase status in the Portuguese population and (iii) self-reported gastrointestinal complaints are not good predictors of the LP status, implying that a significant part of those complaints may not be related to hypolactasia.
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Affiliation(s)
- Licínio Manco
- Research Centre for Anthropology and Health CIAS, Department of Life Sciences, University of Coimbra, 3000 Coimbra, Portugal.
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Abstract
PURPOSE OF REVIEW Relevance of symptom analysis during hydrogen breath test (HBT) for establishing a clinical diagnosis of sugar intolerance is reviewed. RECENT FINDINGS Evaluation of symptoms developed in response to the ingestion of 50 g lactose could represent a simple screening test to select patients for lactose intolerance testing. Patients who do not develop symptoms do not need to be referred for HBT. In addition, symptoms reported by patients during a negative HBT cannot be at all times attributed to a false-negative test; instead, a 'nocebo' effect is likely to be implicated. On the other hand, in a double-blind randomized study, a dose of 25 g fructose was suggested as the most appropriate for testing individuals with suspected fructose malabsorption, whereas symptom reliability to diagnose fructose intolerance was inaccurate. SUMMARY Whereas the development of symptoms after a positive HBT may indicate sugar intolerance, it is still not clear whether the absence of symptoms after sugar malabsorption gives any indication as to the role of that sugar in the genesis of patient's complaints. Further studies should evaluate whether the disappearance of symptoms with a sugar-restricted diet after a positive HBT is a better diagnostic criterion of sugar intolerance than the development of symptoms.
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Affiliation(s)
- Fernando Fernández-Bañares
- Department of Gastroenterology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Hospital Universitary Mutua Terrassa, University of Barcelona, Terrassa, Barcelona, Spain.
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Mendoza Torres E, Varela Prieto LL, Villarreal Camacho JL, Villanueva Torregroza DA. Diagnosis of adult-type hypolactasia/lactase persistence: genotyping of single nucleotide polymorphism (SNP C/T-13910) is not consistent with breath test in Colombian Caribbean population. ARQUIVOS DE GASTROENTEROLOGIA 2012; 49:5-8. [DOI: 10.1590/s0004-28032012000100002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2011] [Accepted: 08/05/2011] [Indexed: 01/23/2023]
Abstract
CONTEXT: Genotyping of single nucleotide polymorphism (SNP C/T-13910) located upstream of the lactase gene is used to determine adult-type hypolactasia/lactase persistence in North-European Caucasian subjects. The applicability of this polymorphism has been studied by comparing it with the standard diagnostic methods in different populations. OBJECTIVE: To compare the lactose hydrogen breath test with the genetic test in a sample of the Colombian Caribbean population. METHODS: Lactose hydrogen breath test and genotyping of SNP C/T-13910 were applied to 128 healthy individuals (mean age 35 ± 1). A positive lactose hydrogen breath test was indicative of hypolactasia. Genotyping was done using polymerase chain reaction/restriction fragment length polymorphism. The kappa index was used to establish agreement between the two methods. RESULTS: Seventy-six subjects (59%) were lactose-maldigesters (hypolactasia) and 52 subjects (41%) were lactose-digesters (lactase persistence). The frequencies of the CC, CT and TT genotypes were 80%, 20% and 0%, respectively. Genotyping had 97% sensitivity and 46% specificity. The kappa index = 0.473 indicates moderate agreement between the genotyping of SNP C/T-13910 and the lactose hydrogen breath test. CONCLUSION: The moderate agreement indicates that the genotyping of the SNP C/T-13910 is not applicable to determine adult-type hypolactasia/lactase persistence in the population participating in this study.
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Marton A, Xue X, Szilagyi A. Meta-analysis: the diagnostic accuracy of lactose breath hydrogen or lactose tolerance tests for predicting the North European lactase polymorphism C/T-13910. Aliment Pharmacol Ther 2012; 35:429-40. [PMID: 22211845 DOI: 10.1111/j.1365-2036.2011.04962.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The diagnostic accuracy of two indirect tests of lactose digestion, lactose breath hydrogen and lactose tolerance tests, have not been systematically reviewed for comparison with available publications on genotype. AIM To perform a meta-analysis of available studies that compares the north-European genetic polymorphism C/T-13910 with the lactose breath hydrogen and the lactose tolerance tests, to determine their ability to predict geno/phenotype relationships. We examine the effects of lactose loading dose, inclusion of children and latitudes of study centre on comparative outcome. METHODS An electronic database of the literature as well as individual references in articles were searched with the theme of genetics of lactase and comparisons with breath or lactose tolerance tests were carried out. Random effect and fixed effect models were used for breath and lactose tolerance tests respectively, to report summary accuracy measures with 95% confidence intervals (CI). RESULTS The search revealed 19 studies: 17 evaluated breath hydrogen, five lactose tolerance test (3/17 overlapped). Overall sensitivity was 0.88 (CI, 0.85-0.90), specificity was 0.85 (CI, 0.82-0.87) for breath test. Heterogeneity was explored by adjusting for studies including children, high or low dose lactose and to some extent by site of study. The lactose tolerance test showed sensitivity of 0.94 (0.9-0.97) and specificity of 0.90 (0.84-0.95) with a nonsignificant heterogeneity. CONCLUSION The diagnostic accuracy of both tests individually reflects expected geno/phenotypes when the populations are well defined.
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Affiliation(s)
- A Marton
- Department of Medicine, MUHC, Montreal General Hospital, McGill University School of Medicine, Montreal, QC, Canada
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35
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Haberkorn BCM, Ermens AAM, Koeken A, Cobbaert CM, van Guldener C. Improving diagnosis of adult-type hypolactasia in patients with abdominal complaints. Clin Chem Lab Med 2011; 50:119-23. [PMID: 21936609 DOI: 10.1515/cclm.2011.716] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2011] [Accepted: 08/28/2011] [Indexed: 01/08/2023]
Abstract
BACKGROUND Adult-type hypolactasia is caused by genetic lactase non-persistence. It is the most common cause of lactose intolerance, which results in gastrointestinal symptoms after ingestion of dairy products. Currently, lactose intolerance is investigated by the hydrogen breath test (HBT), which is considered the preferred diagnostic test. Adult-type hypolactasia may also be diagnosed by genotyping. The single nucleotide polymorphism -13910C>T, which is located upstream of the lactase gene (LCT), is tightly associated with lactase persistence. Several other variants, mostly in non-European populations, can also lead to lactase persistence. This study investigated the accuracy of a modified, recently proposed algorithm which includes genotyping for the diagnosis of adult-type hypolactasia in a patient population with unexplained abdominal complaints. METHODS In 126 patients with unexplained abdominal symptoms or who were suspected to have adult-type hypolactasia, LCT genotyping by melting curve analysis on a LightCycler was performed. Those patients with CC(-13910) genotype (indicating loss of lactase expression) were directly referred to a dietician for a lactose-free diet. Those identified as CT(-13910) or TT(-13910) genotype underwent a HBT. Those who tested positive for hydrogen were also referred to a dietician for a lactose-free diet. The response to diet modification was recorded. RESULTS Genotype prevalences were: CC(-13910): 43 (34.1%); CT(-13910): 48 (38.1%); TT(-13910): 33 (26.2%); TG-13915: 2 (1.6%). Eleven of 48 (23%) patients with CT(-13910)-genotype and 1/33 (3%) patients with TT(-13910)-genotype had a positive hydrogen breath test. They all improved after a lactose-free diet. Four of 43 (9%) patients with CC(-13910)-genotype still had symptoms after a lactose-free diet. CONCLUSIONS The results show that lactase-genotype testing can be used as a first step to diagnose lactose intolerance in a patient population with unexplained abdominal complaints. It accurately identifies the group of patients sensitive to lactose, those who need further breath testing and those in whom adult-type hypolactasia can be excluded with high probability without performing a HBT. This algorithm would save hydrogen breath testing in more than 50% of the patients who present with unexplained abdominal symptoms.
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Abstract
PURPOSE OF REVIEW To summarize the recent progress made in noninvasive monitoring of volatile compounds in exhaled breath and above biological liquids, as they are becoming increasingly important in assessing the nutritional and clinical status and beginning to provide support to conventional clinical diagnostics and therapy. To indicate the potential of these developments in medicine and the specific areas which are currently under investigation. RECENT FINDINGS The significance of the following breath gases and their concentrations are reported: acetone and the influence of diet; ammonia confirmed as an indicator of dialysis efficacy; hydrogen and the (13)CO(2)/(12)CO(2) ratio (following the ingestion of (13)C-labeled compounds) as related to gastric emptying and bowel transit times; hydrogen cyanide released by Pseudomonas and its detection in breath of children with cystic fibrosis; and multiple trace compounds in breath of patients with specific pathophysiological conditions and 'metabolic profiling'. SUMMARY Advanced analytical methods, especially exploiting mass spectrometry, are moving breath analysis towards the clinical setting; some trace gas metabolites are already being exploited in diagnosis and therapy. Much effort is being given to the search for biomarkers of tumours in the body. HCN as an indicator of the presence of Pseudomonas in the airways has real potential in therapeutically alleviating the symptoms of cystic fibrosis.
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Affiliation(s)
- Patrik Španěl
- J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
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Corella D, Arregui M, Coltell O, Portolés O, Guillem-Sáiz P, Carrasco P, Sorlí JV, Ortega-Azorín C, González JI, Ordovás JM. Association of the LCT-13910C>T polymorphism with obesity and its modulation by dairy products in a Mediterranean population. Obesity (Silver Spring) 2011; 19:1707-14. [PMID: 21193851 PMCID: PMC4426982 DOI: 10.1038/oby.2010.320] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The -13910C>T polymorphism (rs4988235) upstream from the lactase (LCT) gene, strongly associated with lactase persistence (LP) in Europeans, is emerging as a new candidate for obesity. We aimed to analyze the association of this polymorphism with obesity-related variables and its modulation by dairy product intake in an elderly population. We studied 940 high-cardiovascular risk Spanish subjects (aged 67 ± 7 years). Dairy product consumption was assessed by a validated questionnaire. Anthropometric variables were directly measured, and metabolic syndrome-related variables were obtained. Prevalence of genotypes was: 38.0% CC (lactase nonpersistent (LNP)), 45.7% CT, and 16.3% TT. The CC genotype was not associated with lower milk or dairy product consumption in the whole population. Only in women was dairy intake significantly lower in CC subjects. The most important association was obtained with anthropometric measurements. CC individuals had lower weight (P = 0.032), lower BMI (29.7 ± 4.2 vs. 30.6 ± 4.2 kg/m(2); P = 0.003) and lower waist circumference (101.1 ± 11.8 vs. 103.5 ± 11.5 cm; P = 0.005) than T-allele carriers. Obesity risk was also significantly higher in T-allele carriers than in CC individuals (odds ratio (OR): 1.38; 95% confidence interval (CI): 1.05-1.81; P = 0.01), and remained significant even after adjustment for sex, age, diabetes, physical activity, and energy intake. However, in subgroup analysis, these associations were found to be significant only among those consuming moderate or high lactose intakes (>8 g/day). No significant associations with lipids, glucose, or blood pressure were obtained after adjustment for BMI. In conclusion, despite not finding marked differences in dairy product consumption, this polymorphism was strongly associated with BMI and obesity and modulated by lactose intake in this Mediterranean population.
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Affiliation(s)
- Dolores Corella
- Department of Preventive Medicine and Public Health, Genetic and Molecular Epidemiology Unit School of Medicine, University of Valencia, Valencia, Spain.
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Kuchay RAH, Thapa BR, Mahmood A, Mahmood S. Effect of C/T -13910 cis-acting regulatory variant on expression and activity of lactase in Indian children and its implication for early genetic screening of adult-type hypolactasia. Clin Chim Acta 2011; 412:1924-30. [PMID: 21763294 DOI: 10.1016/j.cca.2011.06.032] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2011] [Accepted: 06/24/2011] [Indexed: 10/18/2022]
Abstract
BACKGROUND Absorption of milk sugar (lactose) is regulated by the activity of lactase enzyme in gut wall. Intestinal lactase activity declines during childhood in majority of human populations leading to adult-type hypolactasia (primary lactose malabsorption), limiting the use of fresh milk due to lactose intolerance. Aim of this study was to correlate lactase expression and activity with C/T -13910 variant in Indian children, determine the age of onset of down-regulation of lactase activity and assess the applicability of the C/T -13910 variant as a diagnostic marker for identifying children genetically inclined to develop adult-type hypolactasia. METHODS Intestinal biopsies were obtained from 176 children aged 1-16 years undergoing routine endoscopy for various abdominal complaints. The biopsies were assayed for lactase, sucrase and maltase activities and genotyped for C/T 13910 variant using PCR-RFLP analysis. The functional effect of the C/T -13910 variant on expression of lactase mRNA and protein in these children was examined using reverse-transcription PCR and western blotting. RESULTS Among the 176 children investigated in our study, 56.8% (100/176) carried the C/C -13910 genotype, which has been associated with the onset of adult-type hypolactasia, while 40.9% (72/176) carried the C/T -13910 genotype and 2.3% (4/176) the T/T -13910 genotype. There was a significant correlation between lactase activity and C/T -13910 variant (P<0.001). The mean level of lactase activity among children with C/C -13910 genotype was 15.9 U/g protein and with C/T and T/T -13910 genotypes was 30.9 U/g protein. The age of onset of down-regulation of lactase activity in children with C/C -13910 genotype was between 3 and 5 years and keeping 10 U/g protein lactase activity as cut off, adult-type hypolactasia was evident in all the individuals>8 years of age for this genotype. C/C -13910 genotype was associated with low expression of lactase mRNA and protein compared with C/T genotype. Considering lactase activity of 10 U/g protein as gold standard, predictive value of genetic test based on C/T -13910 variant for adult-type hypolactasia was 100% in children>8 years of age. CONCLUSION C/T -13910 cis-acting regulatory variant located ≈14 kb upstream of lactase gene (LCT) completely correlates with lactase phenotype in Indian children. The genetic testing for the C/T -13910 variant may be helpful in the diagnosis of adult-type hypolactasia in Indian children.
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Affiliation(s)
- Raja A H Kuchay
- Department of Biochemistry, Panjab University, Chandigarh, India
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