Association of tumor necrosis factor-α gene promoter polymorphism at sites -308 and -238 with non-alcoholic fatty liver disease: a meta-analysis

Background and aim: Environmental and genetic factors play a role in the pathogenesis and natural history of non-alcoholic fatty liver disease (NAFLD). The objective of this study was to quantitatively evaluate the association between tumor necrosis factor (TNF)-α gene promoter polymorphism at sites -308 and -238 and NAFLD susceptibility.

Methods: We performed an extensive search of relevant studies and made a meta-analysis, including eight studies with 837 NAFLD cases and 990 controls in the association between TNF-α -308 polymorphism and NAFLD; and seven studies with 771 cases and 787 controls in TNF-α -238 polymorphism.

Results: The combined results showed that there was a significant difference in TNF-α-238 genotype distribution between NAFLD and control based on all studies (GA/AA vs GG [odds ratio = 2.06, 95% confidence interval = 1.58-2.69, P < 0.000,01]). However, the combined results based on all studies showed there was no evidence of association of TNF-α-308 genotype distribution between NAFLD cases and controls (GA/AA vs GG [odds ratio = 1.08, 95% confidence interval = 0.82-1.42, P = 0.60]). When stratifying for race, the significant results did not change materially compared with whole populations.

Conclusion: This meta-analysis suggested that TNF-α gene promoter polymorphism at position -238 but not -308 might be a risk factor for NAFLD.