Observational Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Aug 28, 2016; 8(24): 1019-1027
Published online Aug 28, 2016. doi: 10.4254/wjh.v8.i24.1019
Hypolactasia is associated with insulin resistance in nonalcoholic steatohepatitis
Daniel Ferraz de Campos Mazo, Rejane Mattar, José Tadeu Stefano, Joyce Matie Kinoshita da Silva-Etto, Márcio Augusto Diniz, Sebastião Mauro Bezerra Duarte, Fabíola Rabelo, Rodrigo Vieira Costa Lima, Priscila Brizolla de Campos, Flair José Carrilho, Claudia P Oliveira
Daniel Ferraz de Campos Mazo, Rejane Mattar, José Tadeu Stefano, Joyce Matie Kinoshita da Silva-Etto, Márcio Augusto Diniz, Sebastião Mauro Bezerra Duarte, Fabíola Rabelo, Rodrigo Vieira Costa Lima, Priscila Brizolla de Campos, Flair José Carrilho, Claudia P Oliveira, Division of Gastroenterology and Hepatology, Department of Gastroenterology (LIM 07), University of São Paulo School of Medicine, São Paulo 05403-000, Brazil
Author contributions: de Campos Mazo DF, Mattar R and Oliveira CP conceived and designed the study, contributed to the data analysis and interpretation and wrote the manuscript; da Silva-Etto JMK and Mattar R performed the LCT-13910C>T genotyping; de Campos Mazo DF, Stefano JT, Duarte SMB, Rabelo F, Lima RVC and de Campos PB collected and assembled the data; Diniz MA performed the statistical analysis and analyzed the data; Carrilho FJ contributed to the data analysis and interpretation; all authors read and approved the final version of the manuscript.
Institutional review board statement: This study was conducted in accordance with the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Ethics Committee of the Hospital das Clínicas (No. 448520).
Informed consent statement: All involved persons provided their informed consent prior to study inclusion.
Conflict-of-interest statement: The authors declare no conflicts of interest in this work.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Claudia P Oliveira, MD, PhD, Division of Gastroenterology and Hepatology, Department of Gastroenterology (LIM 07), University of São Paulo School of Medicine, Av Dr Eneas de Carvalho Aguiar 255, 9° Andar, Sala 9159, São Paulo 05403-000, Brazil. cpm@.usp.br
Telephone: +55-11-26616447 Fax: +55-11-26617830
Received: April 26, 2016
Peer-review started: April 28, 2016
First decision: May 17, 2016
Revised: June 26, 2016
Accepted: July 14, 2016
Article in press: July 18, 2016
Published online: August 28, 2016
Abstract
AIM

To assess lactase gene (LCT)-13910C>T polymorphisms in Brazilian non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) patients in comparison with healthy controls.

METHODS

This was a transverse observational clinical study with NAFLD patients who were followed at the Hepatology Outpatient Unit of the Hospital das Clínicas, São Paulo, Brazil. The polymorphism of lactase non-persistence/lactase persistence (LCT-13910C>T) was examined by PCR-restriction fragment length polymorphism technique in 102 liver biopsy-proven NAFLD patients (steatosis in 9 and NASH in 93) and compared to those of 501 unrelated healthy volunteers. Anthropometric, clinical, biochemical and liver histology data were analyzed. Continuous variables were compared using the t or Mann-Whitney tests, and categorical data were compared with the Fisher’s exact test. Univariate logistic regression and multivariate logistic regression adjusted for gender and age were performed.

RESULTS

No differences in the LCT-13910 genotype frequencies were noted between the NAFLD patients (66.67% of the patients with steatosis were CC, 33.33% were CT, and none were TT; 55.91% of the patients with NASH were CC, 39.78% were CT, and 4.3% were TT; P = 0.941) and the healthy controls (59.12% were CC, 35.67% were CT, and 5.21% were TT) or between the steatosis and NASH patients. That is, the distribution of the lactase non-persistence/lactase persistence polymorphism (LCT-13910C>T) in the patients with NAFLD was equal to that in the general population. In the NASH patients, the univariate analysis revealed that the lactase non-persistence (low lactase activity or hypolactasia) phenotype was associated with higher insulin levels (23.47 ± 15.94 μU/mL vs 15.8 ± 8.33 μU/mL, P = 0.027) and a higher frequency of insulin resistance (91.84% vs 72.22%, P = 0.02) compared with the lactase persistence phenotype. There were no associations between the LCT genotypes and diabetes (P = 0.651), dyslipidaemia (P = 0.328), hypertension (P = 0.507) or liver histology in these patients. Moreover, in the NASH patients, hypolactasia was an independent risk factor for insulin resistance even after adjusting for gender and age [OR = 5.0 (95%CI: 1.35-20; P = 0.017)].

CONCLUSION

The LCT-13910 genotype distribution in Brazilian NAFLD patients was the same as that of the general population, but hypolactasia increased the risk of insulin resistance in the NASH patients.

Keywords: Lactose intolerance, Genetic polymorphism, Insulin resistance, Non-alcoholic fatty liver disease, Nonalcoholic steatohepatitis

Core tip: Non-alcoholic fatty liver disease (NAFLD) exhibits a close relationship with metabolic syndrome (MetS), but the associations of the lactase non-persistence/lactase persistence genotypes with MetS components are controversial. Therefore, we assessed hypolactasia (LCT-13910CC) and lactase persistence genotypes in 102 Brazilian NAFLD patients in comparison with 501 healthy controls, the associations of these polymorphisms were verified with the results of biochemical tests, MetS and severity of liver histology in nonalcoholic steatohepatitis (NASH) patients. No differences in the LCT-13910C>T polymorphisms were noted between the NAFLD and controls, but hypolactasia increased the risk of insulin resistance in the NASH patients.