I148M variant of PNPLA3-gene is not associated with metabolic syndrome in patients with NAFLD in the Indian ethnicity

Background: Non-alcoholic fatty liver disease (NAFLD) is now considered to precede the development of diabetes and metabolic syndrome (MetS) overriding the earlier notion of NAFLD being the hepatic manifestation of MetS. Studies identified variants conferring enhanced susceptibility to MetS predominantly in lipid metabolism related genes. A variant I148M in PNPLA3 is replicated across ethnicities for its role in NAFLD, however its association with MetS is conflicting. We performed this study to explore its association with MetS. Methods: This is a retro-prospective study that recruited 502 individuals with/without NAFLD based on fatty infiltration (B-type ultrasonography). Demographic/anthropometric data, blood samples were collected. Genotyping was carried out by PCR and direct sequencing. Student's t-test was used for continuous variables. Chisquare test was used to test the association of the variant with MetS. The strength of association was explored by using Odds ratio (95% CI). Multiple logistic regression was used to identify independent predictor variables for metabolic syndrome. Results: Of the 502 that comrised the study group, data pertaining (MetS) to 476 were used for further analysis. The mean age of controls (n = 121) and patients with NAFLD (n = 355) were 38.7 +/- 12.3; 37.8 +/- 9.4 years respectively. A significant difference in the anthropometric and levels of liver enzymes were noted between the groups with higher levels in patients. Association of I148M variant in PNPLA3 gene conferring a 2.29-fold risk of fatty infiltration in the variant carriers was noted. Further, of the 355 with NAFLD, 152 (42.82%) were found to have MetS. There was no association (p = 0.9) of the I148M in PNPLA3 gene with MetS. None of the variables were associated with metabolic syndrome between wild and variant carriers. Conclusion: Although a sizeable number of patients with NAFLD had metabolic syndrome, I148M- PNPLA3 variant was not associated with MetS. However, the I148M variant conferred enhanced susceptibility to fatty infiltration.