SREBP-2 1784 G/C genotype is associated with non-alcoholic fatty liver disease in north Indians

Abstract

Background: Genetics of non-alcoholic fatty liver (NAFLD) in Asian Indians has been inadequately investigated. This study aims to determine the association of the 1784G>C polymorphism in the SREBP-2 gene with NAFLD in Asian Indians in north India.

Methods: In this study, (n=335); 162 obese with NAFLD, 91 obese without NAFLD and 82 non-obese without NAFLD subjects were recruited. Abdominal ultrasound, clinical profile, anthropometry, metabolic profile, serum levels of alanine aminotransferase, aspartate aminotransferase, fasting insulin and high sensitivity C-reactive protein (hs-CRP) were analysed. Polymerase chain reaction and restriction fragment length polymorphism were used to identify individual genotypes, and the association of this polymorphism with clinical and biochemical parameters was assessed.

Results: The observed frequency of G allele was 0.73 and C allele was 0.27. Frequency of C/C genotype was higher in NAFLD as compared to obese and non-obese subjects (p=0.003). In NAFLD subjects 57.4% were G/G homozygous, 31.5% G/C heterozygous and 11.1% were C/C homozygous. The SREBP-2 genotype frequencies deviated from the Hardy Weinberg Equilibrium (X² = 6.39, p = 0.0114). Mean values of TG (p = 0.002), TC (p =0.002), ALT (p =0.04) and AST (p =0.03) levels were significantly higher in NAFLD subjects with G/C genotype as compared to G/G genotypes in obese and non-obese groups. Fasting insulin (p =0.03), HOMA (p =0.009) and hs-CRP levels were significantly higher in NAFLD subjects with G/C genotype as compared to obese and non obese subjects with G/G genotypes.

Conclusion: In this study, conducted for the first time in Asian Indians, SREBP-2 1784 G>C genotype was associated with NAFLD.