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Erkurt M, Kaya A, Kuku İ, Kaya E, Berber İ, Biçim S, Hidayet E, Yağin F, Sarıcı A. The frequency of HLA A, B, C, DP, DQ, DR allele in patients of Turkish and Syrian nationals with allogeneic stem cell transplantation. IRAQI JOURNAL OF HEMATOLOGY 2022. [DOI: 10.4103/ijh.ijh_21_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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Olamoyegun MA, Ala OA. Type 1 diabetes in a Nigerian family - occurrence in three out of four siblings: A case report. World J Diabetes 2019; 10:511-516. [PMID: 31641427 PMCID: PMC6801310 DOI: 10.4239/wjd.v10.i10.511] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 09/04/2019] [Accepted: 09/22/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Most occurrences of type 1 diabetes cases in any population are sporadic rather than familial. Hence, type 1 diabetes among siblings is a rare occurrence. Even more rare is for three or more siblings to develop type 1 diabetes. In this report, we describe a case of a Nigerian family in which type 1 diabetes occurred in three siblings among four children with neither parent having diabetes. All three siblings are positive for glutamic acid decarboxylase and anti-islet cell antibodies.
CASE SUMMARY There were four siblings (three males and one female) born to a couple without a diagnosis of diabetes. The eldest child (male) was diagnosed with diabetes at the age of 15, the second child (female) was diagnosed at the age of 11 and the fourth child (male) was diagnosed at the age of 9. All the siblings presented with similar osmotic symptoms and were diagnosed of diabetic ketoacidosis. All of them had markedly reduced serum C-peptide levels with high levels of glutamic acid decarboxylase and insulinoma-associated protein-2 antibodies. We could not perform genetic analysis of HLA-DR, DQ and CTLA4 in the siblings as well as the parents; hence haplotypes could not be characterized. Both parents of the probands have no prior history of diabetes, and their blood glucose and glycated hemoglobin levels were within normal ranges. The third child (male) has no history suggestive of diabetes, and his blood glucose and glycated hemoglobin have remained within normal ranges.
CONCLUSION Although the occurrence of type 1 diabetes in proband siblings is uncommon, screening for diabetes among siblings especially with islet autoantibodies should be encouraged.
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Affiliation(s)
- Michael Adeyemi Olamoyegun
- Department of Internal Medicine, Endocrinology, Diabetes & Metabolism Unit, College of Health Sciences, Ladoke Akintola University of Technology (LAUTECH)/LAUTECH Teaching Hospital, Ogbomoso 240222, Oyo State, Nigeria
| | - Oluwabukola Ayodele Ala
- Department of Internal Medicine, Endocrinology, Diabetes & Metabolism Unit, BOWEN University Teaching Hospital, and College of Health Sciences, BOWEN University, Iwo 232101, Osun State, Nigeria
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Comparison of Herpes Simplex Virus 1 Strains Circulating in Finland Demonstrates the Uncoupling of Whole-Genome Relatedness and Phenotypic Outcomes of Viral Infection. J Virol 2019; 93:JVI.01824-18. [PMID: 30760568 PMCID: PMC6450105 DOI: 10.1128/jvi.01824-18] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Accepted: 01/23/2019] [Indexed: 12/14/2022] Open
Abstract
Herpes simplex viruses (HSV) infect a majority of adults. Recent data have highlighted the genetic diversity of HSV-1 strains and demonstrated apparent genomic relatedness between strains from the same geographic regions. We used HSV-1 clinical isolates from Finland to test the relationship between viral genomic and geographic relationships, differences in specific genes, and characteristics of viral infection. We found that viral isolates from Finland separated into two distinct groups of genomic and geographic relatedness, potentially reflecting historical patterns of human and viral migration into Finland. These Finnish HSV-1 isolates had distinct infection characteristics in multiple cell types tested, which were specific to each isolate and did not group according to genomic and geographic relatedness. This demonstrates that HSV-1 strain differences in specific characteristics of infection are set by a combination of host cell type and specific viral gene-level differences. A majority of adults in Finland are seropositive carriers of herpes simplex viruses (HSV). Infection occurs at epithelial or mucosal surfaces, after which virions enter innervating nerve endings, eventually establishing lifelong infection in neurons of the sensory or autonomic nervous system. Recent data have highlighted the genetic diversity of HSV-1 strains and demonstrated apparent geographic patterns in strain similarity. Though multiple HSV-1 genomes have been sequenced from Europe to date, there is a lack of sequenced genomes from the Nordic countries. Finland’s history includes at least two major waves of human migration, suggesting the potential for diverse viruses to persist in the population. Here, we used HSV-1 clinical isolates from Finland to test the relationship between viral phylogeny, genetic variation, and phenotypic characteristics. We found that Finnish HSV-1 isolates separated into two distinct phylogenetic groups, potentially reflecting historical waves of human (and viral) migration into Finland. Each HSV-1 isolate harbored a distinct set of phenotypes in cell culture, including differences in the amount of virus production, extracellular virus release, and cell-type-specific fitness. Importantly, the phylogenetic clusters were not predictive of any detectable pattern in phenotypic differences, demonstrating that whole-genome relatedness is not a proxy for overall viral phenotype. Instead, we highlight specific gene-level differences that may contribute to observed phenotypic differences, and we note that strains from different phylogenetic groups can contain the same genetic variations. IMPORTANCE Herpes simplex viruses (HSV) infect a majority of adults. Recent data have highlighted the genetic diversity of HSV-1 strains and demonstrated apparent genomic relatedness between strains from the same geographic regions. We used HSV-1 clinical isolates from Finland to test the relationship between viral genomic and geographic relationships, differences in specific genes, and characteristics of viral infection. We found that viral isolates from Finland separated into two distinct groups of genomic and geographic relatedness, potentially reflecting historical patterns of human and viral migration into Finland. These Finnish HSV-1 isolates had distinct infection characteristics in multiple cell types tested, which were specific to each isolate and did not group according to genomic and geographic relatedness. This demonstrates that HSV-1 strain differences in specific characteristics of infection are set by a combination of host cell type and specific viral gene-level differences.
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Alper CA, Larsen CE, Trautwein MR, Alford DR. A stochastic epigenetic Mendelian oligogenic disease model for type 1 diabetes. J Autoimmun 2018; 96:123-133. [PMID: 30309752 DOI: 10.1016/j.jaut.2018.09.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 09/12/2018] [Indexed: 01/14/2023]
Abstract
The incidence of type 1 diabetes (T1D) and some other complex diseases is increasing. The cause has been attributed to an undefined changing environment. We examine the role of the environment (or any changing non-genetic mechanism) in causing the rising incidence, and find much evidence against it: 1) Dizygotic twin T1D concordance is the same as siblings of patients in general; 2) If the environment is responsible for both the discordance among identical twins of patients with T1D and its rising incidence, the twin concordance rate should be rising, but it is not; 3) Migrants from high-to low-incidence countries continue to have high-incidence children; 4) TID incidence among the offspring of two T1D parents is identical to the monozygotic twin rate. On the other hand, genetic association studies of T1D have revealed strong susceptibility in the major histocompatibility complex and many optional additive genes of small effect throughout the human genome increasing T1D risk. We have, from an analysis of previously published family studies, developed a stochastic epigenetic Mendelian oligogenic (SEMO) model consistent with published observations. The model posits a few required recessive causal genes with incomplete penetrance explaining virtually all of the puzzling features of T1D, including its rising incidence and the specific low T1D incidence rates among first-degree relatives of patients. Since historic selection against any causal gene could prevent T1D, we postulate that the rising incidence is because of increasing population mixing of parents from some previously isolated populations that had selected against different causal genes.
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Affiliation(s)
- Chester A Alper
- Program in Cellular and Molecular Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA; Department of Pediatrics, Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA.
| | - Charles E Larsen
- Program in Cellular and Molecular Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA; Department of Pediatrics, Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA
| | - Michael R Trautwein
- Program in Cellular and Molecular Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA
| | - Dennis R Alford
- Program in Cellular and Molecular Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA
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Mayer-Davis EJ, Kahkoska AR, Jefferies C, Dabelea D, Balde N, Gong CX, Aschner P, Craig ME. ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 2018; 19 Suppl 27:7-19. [PMID: 30226024 PMCID: PMC7521365 DOI: 10.1111/pedi.12773] [Citation(s) in RCA: 362] [Impact Index Per Article: 51.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Accepted: 07/27/2018] [Indexed: 12/16/2022] Open
Affiliation(s)
- Elizabeth J. Mayer-Davis
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Anna R. Kahkoska
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Craig Jefferies
- Starship Children’s Hospital, Auckland District Health Board, Auckland, New Zealand
| | - Dana Dabelea
- Department of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, Colorado
| | - Naby Balde
- Department of Endocrinology, University Hospital, Conakry, Guinea
| | - Chun X. Gong
- Beijing Children’s Hospital, Capital Medical University, Beijing, China
| | | | - Maria E. Craig
- The Children’s Hospital at Westmead, University of Sydney, Sydney, New South Wales, Australia,School of Women’s and Children’s Health, University of NSW, Sydney, New South Wales, Australia
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Craig ME, Jefferies C, Dabelea D, Balde N, Seth A, Donaghue KC. ISPAD Clinical Practice Consensus Guidelines 2014. Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 2014; 15 Suppl 20:4-17. [PMID: 25182305 DOI: 10.1111/pedi.12186] [Citation(s) in RCA: 177] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 06/16/2014] [Indexed: 12/20/2022] Open
Affiliation(s)
- Maria E Craig
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead and University of Sydney, Sydney, Australia; School of Women's and Children's Health, University of New South Wales, Sydney, Australia
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Abstract
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by absolute insulin deficiency resulting from the progressive immune-mediated destruction of pancreatic islet beta cells. It is thought to be triggered by as yet unidentified environmental factors in genetically susceptible individuals, the major genetic contribution coming from loci within the HLA complex, in particular HLA class II. The worldwide incidence of T1D varies by at least 100-fold, being highest in Finland and Sardinia (Italy) and lowest in Venezuela and China. The incidence has been increasing worldwide at an annual rate of approximately 3%. While genetic factors are thought to explain some of the geographic variability in T1D occurrence, they cannot account for its rapidly increasing frequency. Instead, the declining proportion of newly diagnosed children with high-risk genotypes suggests that environmental pressures are now able to trigger T1D in genotypes that previously would not have developed the disease during childhood. Although comparisons between countries and regions with low and high-incidence rates have suggested that higher socioeconomic status and degree of urbanization are among the environmental factors that play a role in the rising incidence of T1D, the findings are too inconsistent to allow firm conclusions. Morbidity and mortality as well as causes of death also show considerable geographic variation. While glycemic control has been identified as a major predictor of the micro- and macrovascular complications of T1D and shows considerable geographical variability, it does not appear to be the only factor involved in the regional differences in complication rates. The role of genetics in susceptibility to nephropathy, retinopathy and other diabetic complications largely remains to be explored.
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Craig ME, Hattersley A, Donaghue KC. Definition, epidemiology and classification of diabetes in children and adolescents. Pediatr Diabetes 2009; 10 Suppl 12:3-12. [PMID: 19754613 DOI: 10.1111/j.1399-5448.2009.00568.x] [Citation(s) in RCA: 170] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Affiliation(s)
- Maria E Craig
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Australia.
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Craig ME, Hattersley A, Donaghue K. ISPAD Clinical Practice Consensus Guidelines 2006-2007. Definition, epidemiology and classification. Pediatr Diabetes 2006; 7:343-51. [PMID: 17212603 DOI: 10.1111/j.1399-5448.2006.00216.x] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Affiliation(s)
- Maria E Craig
- University of NSW, The Children's Hospital at Westmead, Australia
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Mimbacas A, Pérez-Bravo F, Santos JL, Pisciottano C, Grignola R, Javiel G, Jorge AM, Cardoso H. The association between HLA DQ genetic polymorphism and type 1 diabetes in a case-parent study conducted in an admixed population. Eur J Epidemiol 2005; 19:931-4. [PMID: 15575351 DOI: 10.1007/s10654-004-5176-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Susceptibility to the type 1 diabetes is genetically controlled and there is an increased risk associated with the presence of some specific alleles of the human leukocyte antigens class II loci (DQA1 and DQB1 genes). The purpose of this study is to evaluate the association between type 1 diabetes and HLA DQ alleles using case-parents trios in the admixed population of Uruguay composed by a mixture of Caucasian, Amerindian and Negroid populations. DQA1 and DQB1 genotyping was performed by polimerase chain reaction followed by oligospecific probes hybridization in 51 case-parents trios. The transmission disequilibrium test was used for detecting differential transmission in the HLA DQ loci. DQB1*0302 was the only allele for which preferential transmission is suggested (probability of transmission = 67.56%; exact p-value TDT = 0.047 uncorrected for multiple comparisons). DQA1*0301 allele showed a trend for preferential transmission without achieving statistical significance. This result would confirm the hypothesis previously advanced in a case-control study. Therefore, DQB1*0302 allele could be considered as the most important susceptibility allele for developing type 1 diabetes in Uruguay population.
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Affiliation(s)
- Adriana Mimbacas
- Departamento de Citogenética, Unidad Asociada, Instituto de Biología, Facultad de Ciencias, Uruguay.
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Kukko M, Virtanen SM, Toivonen A, Simell S, Korhonen S, Ilonen J, Simel O, Knip M. Geographical variation in risk HLA-DQB1 genotypes for type 1 diabetes and signs of beta-cell autoimmunity in a high-incidence country. Diabetes Care 2004; 27:676-81. [PMID: 14988284 DOI: 10.2337/diacare.27.3.676] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To assess possible differences in the frequency of HLA-DQB1 risk genotypes and the emergence of signs of beta-cell autoimmunity among three geographical regions in Finland. RESEARCH DESIGN AND METHODS The series comprised 4,642 children with increased HLA-DQB1-defined genetic risk of type 1 diabetes from the Diabetes Prediction and Prevention (DIPP) study: 1,793 (38.6%) born in Turku, 1,646 (35.5%) in Oulu, and 1,203 (25.9%) in Tampere. These children were examined frequently for the emergence of signs of beta-cell autoimmunity, for the primary screening of which islet cell antibodies (ICA) were used. If the child developed ICA, all samples were also analyzed for insulin autoantibodies (IAA), GAD65 antibodies (GADA), and antibodies to the IA-2 molecule (IA-2A). RESULTS The high- and moderate-risk genotypes were unevenly distributed among the three areas (P<0.001); the high-risk genotype was less frequent in the Oulu region (20.4%) than in the Turku (28.4%; P<0.001) or Tampere regions (27.2%; P<0.001). This genotype was associated with an increased frequency of ICA seroconversion relative to the moderate risk genotypes (hazard ratio 1.89, 95% CI 1.36-2.62). Seroconversions to ICA positivity occurred less commonly in Tampere than in Turku (0.47, 0.28-0.75), whereas the seroconversion rate in Oulu did not differ from that in Turku (0.72, 0.51-1.03). The Tampere-Turku difference persisted after adjustment for risk genotypes, sex, and time of birth (before January 1998 versus later). Seroconversion for at least one additional autoantibody was also less frequent in Tampere than in Turku (0.39, 0.16-0.82). CONCLUSIONS These data show that in Finland, the country with the highest incidence of type 1 diabetes in the world, both the frequency of the high-risk HLA-DQB1 genotype and the risk of seroconversion to autoantibody positivity show geographical variation. The difference in seroconversion rate could not be explained by the difference in HLA-DQB1-defined disease susceptibility, implying that the impact of environmental triggers of diabetes-associated autoimmunity may differ between the three regions studied.
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Affiliation(s)
- Marika Kukko
- Juvenile Diabetes Research Foundation Center for the Prevention of Type 1 Diabetes in Finland, Tampere, Finland
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Geranton S, Rostagnat-Stefanutti A, Bendelac N, Cerrato E, Barbalat V, Leissner P, Nicolino M, Thivolet C, Mougin B. High-risk genotype for type 1 diabetes: a new simple microtiter plate-based ELOSA assay. GENETIC TESTING 2003; 7:7-12. [PMID: 12820696 DOI: 10.1089/109065703321560877] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
The main contribution to genetic susceptibility for type 1 diabetes (T1D) is conferred by the HLA class II genes, with a major involvement of the DQB1*02 and 0302 alleles. The aim of our study was to develop a simple and rapid method suitable for identifying individuals with an HLA-associated T1D risk using whole blood as a source of DNA and reverse hybridization on microtiter plates (ELOSA). DNA was extracted from whole blood using various extraction methods. The PCR-amplified second exon of the DQB1 gene was hybridized at 37 degrees C for 1 hr to a set of 11 capture probes immobilized on a microtiter plate (eight-well strip per test) and corresponding to T1D susceptibility (S), protection (P), or neutral (N) alleles. Colorimetric analysis was then performed using specific oligonucleotides coupled to horseradish peroxidase and OrthoPhenyl Peroxidase (OPD) substrate. DNA samples corresponding to French (Rhône-Alpes area) T1D patients (n = 128) have been genotyped with the HLA-T1D prototype. A strong correlation is observed between susceptible genotypes and the disease, because 92.2% of the T1D individuals screened have at least one susceptible allele (DQB1*02 or *0302), thereby strengthening interest in analyzing DQB1 alleles as HLA-linked T1D markers in our Rhône-Alpes area population. Interestingly, clear T1D-associated genotyping results have been observed when using DNA samples extracted from dried blood spots, making it possible to envisage such genotyping in geographically dispersed affected families, for large-scale newborn screening, and for the inclusion of high-risk patients in clinical trials aimed at preventing the disease.
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Affiliation(s)
- S Geranton
- INSERM 449, Faculté de Médecine RTH Laennec, 69372 Lyon, France
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Laaksonen M, Pastinen T, Sjöroos M, Kuokkanen S, Ruutiainen J, Sumelahti ML, Reijonen H, Salonen R, Wikström J, Panelius M, Partanen J, Tienari PJ, Ilonen J. HLA class II associated risk and protection against multiple sclerosis-a Finnish family study. J Neuroimmunol 2002; 122:140-5. [PMID: 11777553 DOI: 10.1016/s0165-5728(01)00456-8] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
We analyzed the HLA class II haplotypes in 249 Finnish nuclear families and compared the frequencies of parental haplotypes transmitted or non-transmitted to multiple sclerosis (MS) patients. The most important predisposing haplotype was DRB1*15-DQB1*0602 (P<10(-6)) as expected and a weak predisposing effect of DRB1*04-DQB1*0302 was revealed after the elimination of DRB1*15-DQB1*0602. HLA-DRB1*01-DQB1*0501 and DRB1*13-DQB1*0603 were negatively associated with MS in transmission disequilibrium test, but only the DRB1*13-DQB1*0603 association remained significant (P=0.008) after the elimination of DRB1*15-DQB1*0602 haplotypes. Based on this study HLA class II haplotypes exhibit both predisposing and protective effects in MS.
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Affiliation(s)
- Mikko Laaksonen
- Turku Immunology Centre and Department of Virology, University of Turku, Kiinamyllynkatu 13, FIN-20520, Turku, Finland
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Petrone A, Bugawan TL, Mesturino CA, Nisticò L, Galgani A, Giorgi G, Cascino I, Erlich HA, Di Mario U, Buzzetti R. The distribution of HLA class II susceptible/protective haplotypes could partially explain the low incidence of type 1 diabetes in continental Italy (Lazio region). TISSUE ANTIGENS 2001; 58:385-94. [PMID: 11929589 DOI: 10.1034/j.1399-0039.2001.580607.x] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
HLA class II is the primary susceptibility gene to type 1 diabetes and the analysis of HLA class II association could help to clarify the relative weight of genetic contribution to the incidence of the disease. Here we present an extensive typing for HLA class II alleles and their haplotypes in a homogenous population of type 1 diabetic patients (n=134) and controls (n=128) and in simplex (n=100) and multiplex families (n=50) from continental Italy (Lazio region). Among the various haplotypes tested, the DRB1*0301-DQA1*0501-DQB1*0201 was the most frequent found in type 1 diabetic patients and was transmitted in 82% of affected siblings, whereas DRB1*0402-DQA1*0301-DQB1*0302 appeared to have the highest odds ratio (10.4), this haplotype was transmitted in 96.3% of affected siblings, followed by DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0405-DQA1*0301-DQB1*0201, DRB1*0401-DQA1*0301-DQB1*0302 and DRB1*0404-DQA1*0301-DQB1*0302. The following haplotypes showed a significant decreased transmission to diabetic siblings: DRB1*0701-DQA1*0201-DQB1*0303, DR2-DQA1*01-DQB1*0602, DR5-DQA1*0501-DQB1*0301. We suggest that the HLA DR/DQ haplotype/genotype frequencies observed could in part explain the low incidence of type 1 diabetes registered in Lazio region (8.1/100.000/year), for a number of reasons: i) the low frequency, in the general control population, of the most susceptible haplotypes and genotype for type 1 diabetes DRB1*0301-DQA1*0501-DQB1*0201 (14%), and DR4-DQA1*0301-DQB1*0302 (9%) and DRB1*0301-DQA1*0501-DQB1*0201/DR4-DQA1*0301-DQB1*0302 (0.8%) compared to other countries characterised by high incidence rate of the disease, Sardinia and Finland, respectively; ii) a significant lower ratio, in the control population, between the susceptible DRB1*0301-DQA1*0501-DQB1*0201 and the neutral DRB1*0701-DQA1*0501-DQB1*0201 haplotypes compared to the Sardinian population; iii) the high frequency of protection haplotypes/genotypes as the DR5-DQA1*0501-DQB1*0301, and DR5-DQA1*0501-DQB1*0301/DR5-DQA1*0501-DQB1*0301 very common in the control population of Lazio region and the DRB1*1401-DQA1*0101-DQB1*0503 haplotype.
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Affiliation(s)
- A Petrone
- Endocrinologia, Dipartimento di Scienze Cliniche, University of Rome La Sapienza, Viale del Policlinico 155, 00161 Rome, Italy
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