Association of Genetic Non-alcoholic Fatty Liver Disease with Insulin Resistance-Are we Different?

Introduction: Metabolic risk factors such as obesity, insulin resistance, type 2 diabetes mellitus and dyslipidemia are associated with non-alcoholic fatty liver disease (NAFLD). In the development and progression of NAFLD genetic mutations also play a significant role. NAFLD associated with the rs 738409 polymorphism of patatin-like phospholipase domain containing 3 gene (PNPLA3) G allele does not feature the typical metabolic abnormalities of NAFLD, including insulin resistance. In the light of rising epidemic of metaobesity in our population this study aimed to evaluate the relation of PNPLA3 polymorphism with insulin resistance.

Methods: In this case control hospital based study, 100 patients of NAFLD were recruited based on ultrasound findings of hepatic steatosis. Healthy subjects age and gender matched(n = 100) from the institute who volunteered to be part of the study were recruited as controls based on the sole criteria of the absence of fatty liver on ultrasonography and normal alanine and aspartate transaminases (ALT and AST) levels. Anthropometry, biochemical profiles and insulin resistance by homeostatic model assessment of insulin resistance (HOMA-IR) were assessed.

Results: A higher frequency of CG and GG genotypes of rs738409 polymorphism of PNPLA3 was observed in patients with NAFLD than controls. These patients with G allele had increased ALT, dyslipidemia and insulin resistance. The polymorphism had positive correlation with severity of hepatic steatosis.

Conclusion: The presence of the PNPLA3 G allele is associated with a risk of NAFLD. Our study shows that subjects with variant PNPLA3 are not only at increased risk for the development and progression of NAFLD, but also have increased insulin resistance.