PNPLA3 I148M Polymorphism in Patients with Nonalcoholic Fatty Liver Disease, Obesity and Prediabetes

Abstract

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance, and therefore predisposes to type 2 diabetes and cardiovascular diseases. Lipid deposition in the liver seems to be critical in the pathogenesis of NAFLD. A common genetic variant, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) has been associated with NAFLD. The aim of the present study was to evaluate the association between PNPLA3, key gene of lipid metabolism and the metabolic traits in obesity NAFLD patients with and without prediabetes. Methods: A total of 208 obese NAFLD patients without (n=125) and with prediabetes (n=83) were included. The genotyping of PNPLA3 I148M variant (rs738409) was performed by restriction analysis. Results: Regarding rs738409 (I148M) polymorphism, CG genotype was positively correlated with prediabetes, insulin resistance, dyslipidemia and metabolic syndrome compared to the wild CC genotype. The carriers of the PNPLA3 I148M variant have 9.6-fold higher risk of glucose disturbances compared to wild genotype (OR 9.649, 95%CI 2.100-44.328, р=0.004). The carriers of the PNPLA3 I148M variant also have a 3 times higher risk for the presence of metabolic syndrome (OR 2.939, 95% CI: 1.590-5.434, p=0.001) and a 2.1-fold higher risk for the presence of insulin resistance (OR 2.127, 95% CI: 1.078-4.194, p=0.029). Conclusions: PNPLA3 I148M is associated with increased risk of prediabetes, metabolic syndrome and insulin resistance in obese patients with NAFLD.