Glucokinase receptor genetic polymorphism in Indian population and its association with Non Alcoholic Fatty Liver Disease

Abstract

Background and Aim: Non Alcoholic Fatty Liver Disease (NAFLD) is now the most important cause of Chronic Liver Disease (CLD) in both Western and Asian population. While some avenues are yet to be explored, underlying cause appears to be the explosive epidemic of metabolic syndrome and obesity in particular. However, the relation between the two is still not completely elucidated. Understanding the genetic background may have relevance to surveillance, therapeutic strategies and in developing preventive measures. There are limited studies on genetic background of NAFLD in Asian population. We attempted to study one such genetic variation, Glucokinase regulator gene (GCKR) in NAFLD patients in Indian population. We aimed to find the association of GCKR gene variants (rs780094, rs1260326) in patients with NAFLD in Indian population and to assess the relation of GCKR variants with clinical profile. Methods: A cross sectional analytical study was conducted in the Department of Gastroenterology at a tertiary care centre in western India. Total 100 subjects between the age group of 18-65 were included in the study. Out of which, 50 were patients with NAFLD including fatty liver, Non Alcoholic Steatohepatitis (NASH) and NASH related cirrhosis and 50 were healthy subjects (No NAFLD). Results: GCKR rs780094 minor allele A was more common in NAFLD patients as compared to healthy subjects. (p= 0.00001). Within the spectrum of NAFLD, A allele was present more commonly among cirrhotics and in NAFLD patients as compared to Non-alcoholic steatohepatitis (NASH) and fatty liver. (p=0.00001). Morbidly obese individuals showed significant association with homozygous A allele (p=0.028). These results were not seen with GCKR rs1260326 across all alleles. Conclusions: GCKR genetic variant rs780094 appears to be significantly associated with NAFLD in Indian population.