Association of metabolic syndrome and patatin-like phospholipase 3 - rs738409 gene variant in non-alcoholic fatty liver disease among a Chennai-based south Indian population.

Background: Non-alcoholic fatty liver disease (NAFLD) is commonly diagnosed in patients presenting with metabolic syndrome (MetS) and has been associated with single nucleotide polymorphisms of rs738409 in the patatin-like phospholipase domain containing 3 (PNPLA3) gene. This association remains to be investigated in the South Indian population. We aimed to determine the association of the PNPLA3 rs738409 gene polymorphism with MetS and NAFLD among a Chennai-based population.

Methods: The study comprised 105 NAFLD cases and 102 controls. All subjects were genotyped for the PNPLA3 rs738409 variant and MetS was defined according to the National Cholesterol Education Program - Adult Treatment Panel III criteria. Our case-control study showed the association of the variant with NAFLD and MetS.

Results: The PNPLA3 rs738409 variant was associated with NAFLD and the genotype frequencies (CC/CG/GG) were 19 (18.1%), 50 (47.6%) and 36 (34.3%) in the NAFLD group and 59 (57.8%), 29 (28.4%) and 14 (13.7%) in the control group respectively. We also confirmed the interaction between the PNPLA3 rs738409 polymorphism and MetS with respect tto elevated triglyceride levels. However, an association with elevated waist circumference, fasting glucose, blood pressure and decreased high-density lipoprotein cholesterol was not observed in the present study.

Conclusions: The PNPLA3 rs738409 gene polymorphism increases the risk of NAFLD by up to four-fold in subjects with an elevated level of triglyceride independent of other features of MetS.