TNF-α −308 polymorphisms and male infertility risk: A meta-analysis and systematic review

This study aimed to conduct a systematic review and meta-analysis of prospective studies discussing TNF-α −308 polymorphism and male infertility. This study was conformed to Preferred Reported Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase and Scopus databases were searched to identify relevant studies by two independent reviewers. Hazard ratios were pooled using fixed-effect or random-effects models when appropriate. Q-test was performed to evaluate study heterogeneity and publication bias appraised using funnel plots. The search yielded five studies (three of Caucasians ethnicity and 2 of Asian ethnicity) comprising 2939 men (2262 infertile men and 677 fertile controls). Most of the studied cases were carried out on TNF-α promoter region at positions −308 G/A (four studies) where −308 C/T was dealt with in one study. Overall, significant associations between TNF-α −308 gene polymorphisms and idiopathic male infertility risk were observed (fixed effect: OR = 0.472, 95% CI: 0.378–0.589; P = 0.001; random effect: OR = 0.407, 95% CI: 0.211–0.785; P = 0.007) with robust findings according to sensitivity analyses. Funnel plot inspections did not give evidences of publication bias. A stratified analysis performed for ethnic groups revealed significant association in both Caucasian and Asian populations. It is concluded that there are evidences of associations between TNF-α −308 gene polymorphisms and male infertility risk.