PNPLA3 rs738409 Polymorphism Associated with Hepatic Steatosis and Advanced Fibrosis in Patients with Chronic Hepatitis C Virus: A Meta-Analysis

Abstract

Background/Aims: The recognition of a correlation between patatin-like phospholipase domain containing-protein 3 (PNPLA3) rs738409 (C>G) and the severity of liver steatosis or fibrosis in chronic hepatitis C (CHC) has not reached a consensus. This meta-analysis sought to investigate with accuracy the association between the PNPLA3 rs738409 (C>G) polymorphism and liver steatosis and advanced fibrosis in CHC patients. Methods: We performed a comprehensive literature search from the PubMed, Embase, Web of Science, and Google Scholar databases up to December 31, 2014. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical analyses were performed using Stata 12.0 software. Results: The meta-analysis revealed the severity of liver fibrosis was significantly higher in CHC patients with PNPLA3 rs738409 GG in Caucasians (versus CC+CG: OR, 2.29; 95% CI, 1.57 to 3.35; p<0.05) but not Asian populations. In Caucasians, liver steatosis was also more severe in CHC patients with rs738409 GG (versus CC+CG; OR, 4.33; 95% CI, 2.59 to 7.22; p<0.05). The sensitivity analysis indicated the results of this meta-analysis were stable and no publication bias was detected. Conclusions: PNPLA3 rs738409 (C>G) was associated with the risk of both advanced liver fibrosis and steatosis in patients with CHC, especially among Caucasian populations. (Gut Liver 2016;10:456-463)

Association of PNPLA3 rs738409 polymorphism with liver steatosis but not with cirrhosis in patients with HBV infection: Systematic review with meta‐analysis

“…Previous studies showed that PNPLA3 variations, especially the rs738409 polymorphism, are associated with hepatic fibrosis and steatosis among CHC patients . PNPLA3 rs738409 SNP can cause hepatic inflammation and consequently lead to fibrosis pathogenesis .…”

Combined effects of the PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7 rs641738 variants on NAFLD severity: a multicenter biopsy-based study

“…The PNPLA3 (patatin-like phospholipase domain containing 3, also known as adiponutrin) p.I148M polymorphism is commonly regarded to be the risk factor for both increased fat accumulation and fibrosis (5,6). The association with steatosis was demonstrated in several candidate studies, whereas the link between PNPLA3 and liver scarring was substantiated by meta-analyses in patients with chronic hepatitis C virus (HCV) infection (7) and in alcoholics (8). The data concerning the involvement of TM6SF2 (transmembrane 6 superfamily member 2) in liver injury are less definitive.…”

PNPLA3 gene in liver diseases

“…in a recent meta-analysis [36] (Table 1). Interestingly, the impact of the SNP seems to be lower compared to fatty liver diseases, as indicated by the lower odds-ratios (OR) observed in carriers of rs738409 [G] with histological damage phenotypes in this etiology.…”