Association of the rs738409 polymorphism in PNPLA3 with development and severity of non-alcoholic fatty liver disease in ethnic Bengali population of West Bengal

Background and Objectives Non-alcoholic Fatty Liver Disease (NAFLD) is a common disorder with a complex etiology. Polymorphic variant rs738409 (Ile148Met) in the PNPLA3 gene has been reported to be associated with NAFLD among several ethnic populations. The present study aims to identify the potential association of this PNPLA3 gene variant with NAFLD among the ethnic Bengali population of West Bengal and correlate it with disease severity and biochemical parameters. Materials and Methods The Ile148Met variant was genotyped among 99 clinically diagnosed NAFLD cases and 100 ethnicity-matched controls from West Bengal using PCR-RFLP-based techniques. Results We identify statistically significant differences in genotype and allele frequencies of rs738409 between NAFLD cases and controls (P = 0.001 & 0.0057). The frequency distribution of risk genotype (GG) and risk allele (G allele) was significantly associated with a higher FIB-4 score (P = 0.0251) and Controlled Attenuation Parameter (CAP) score (P = 0.0072) but not with Liver Stiffness Measurement (LSM) value. The mean CAP score was significantly higher among the risk allele (G allele) carrier than the ‘C’ allele carrier (272.49±51.99 vs 247.38±49.46; P = 0.0328). In patients with NAFLD, the CC genotype was associated with a higher level of total bilirubin (P = 0.0189). Conclusion The Ile148Met variant of the PNPLA3 gene is a predisposing risk factor for the development of NAFLD and is associated with increased severity of hepatic steatosis among the ethnic Bengali population of West Bengal.