PNPLA3 As a Genetic Predictor of Histopathological Severity by Liver Biopsy in Non Alcoholic Fatty Liver Disease

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is defined by widespread steatosis within hepatocytes. The pathogenesis of NAFLD is not fully recognised. It is NAFLD is driven by genetic, environmental, and metabolic factors. Moreover, earlier studies have showed that some polymorphisms raise the possibility of NAFLD. The association between the risk of NAFLD and the patatin-like phospholipase domain-containing 3 (PNPLA3) gene was the most consistently observed.
Aim: To evaluate the effect of the rs738409 polymorphism of the PNPLA3 gene (encoding I148m) on NAFLD.
Patients and Methods: This study involved 30 participants, comprising 20 cases with NAFLD and 10 healthy individuals who served as a control group. The diagnosis was based on liver biopsies obtained during surgery from patients undergoing bariatric surgery or as part of the pre-donation evaluation process for liver transplantation candidates. The PNPLA3 gene variant (rs738409 C/G) was genotyped in blood cells using the TaqMan assay and quantitative polymerase chain reaction (qPCR). Results: Analysis of the PNPLA3 gene variant (rs738409 C/G) distribution revealed a greater prevalence of the heterozygous rs738409 CG and homozygous rs738409 GG variants among NAFLD cases compared to the control group (p = 0.048). Moreover, NAFLD patients carrying the homozygous GG variant showed a significantly increased incidence of hepatic fibrosis (p = 0.018). Additionally, PNPLA3 gene polymorphism emerged as a significant predictor of both liver steatosis and fibrosis in NAFLD cases (p-value equal 0.033 and p-value less than 0.001, correspondingly).
Conclusion: The PNPLA3 rs738409 polymorphism is strongly related to both the risk and severity of non-alcoholic fatty liver disease.