Association of tumor necrosis factor-α gene polymorphisms with risk of non-alcoholic fatty liver disease: Systematic review with meta-analysis

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases that is affected by various environmental and genetic factors. The association between tumor necrosis factor-alpha (TNF-α) gene polymorphism in regions -308G/A (rs1800629) and -238G/A (rs361525) and susceptibility to NAFLD is controversial. Objective: This meta-analysis evaluated the association between different candidate TNF-α polymorphisms and NAFLD. Methodology: A systematic search was conducted on PubMed, Cochrane Library, and Egyptian Knowledge Bank accessing the following databases: Scopus, Web of science, EBSCO and Ovid, and EMBASE to retrieve all relevant studies published until March 29, 2023. Based on predetermined selection criteria, all eligible studies were included in the meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. Results: The systematic search revealed that five TNF-alpha polymorphisms were studied concerning NAFLD risk: TNF-α -1031(rs1799964), -857(rs1799724), -308(rs1800629), -238(rs361525), and -863(rs1800630), with the last three polymorphisms were eligible for meta-analysis. Eleven studies with 1155 NAFLD cases and 1364 controls demonstrated the significant association between rs1800629 polymorphism and NAFLD under both the dominant model [OR = 1.27, 95% CI = 1.01–1.59, P = 0.04] and allelic contrast [OR = 1.26, 95% CI = 1.03–1.54, P = 0.02], with no significant association under heterozygous comparison. Considering the rs361525 polymorphism, meta-analysis including nine studies with 904 cases and 848 controls suggested significant association under each of the dominant model [OR = 1.76, 95% CI = 1.14–2.71, P =0.01], heterozygous model [OR = 1.77, 95% CI = 1.14–2.74, P = 0.01], and the allelic model [OR = 1.66, 95% CI = 1.31–2.44, P = 0.01]. However, no association was found between rs1800630 polymorphism and NAFLD risk. Conclusion: This meta-analysis suggested that TNF-α gene polymorphisms rs361525 and rs1800629, but not rs1800630, might be a risk factor for NAFLD.