Associations of Tumor Necrosis Factor Alpha Gene Polymorphisms and Ankylosing Spondylitis Susceptibility: A Meta-analysis Based on 35 Case-control Studies

Background: Scores of studies on tumor necrosis factor alpha (TNF-alpha) gene polymorphisms and AS have been performed with inconsistent results. The purpose of this study was to provide some more convincing evidence on the associations of TNF-a polymorphisms and AS by using a meta-analysis approach. Methods: Potentially relevant studies were identified from Web of Science, PubMed, EMBASE, Wanfang, and CNKI from inception to March 5, 2020. Newcastle-Ottawa Scale (NOS) was utilized to appraise the quality of included studies. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to assess the strength of the associations under five genetic models. Results: Thirty-five studies with 37 independent cohorts in total were included in the meta-analysis. Based upon NOS, eligible studies were in moderate- to high quality. The merged data suggested rs1799724 polymorphisms were significantly correlated with a reduced risk of AS (C vs. T, OR = 0.55, 95%CI 0.38-0.79, P < .001, P-Bon = 0.005, P-FDR = 0.003). Subgroup analysis by ethnicity indicated that rs1800629 polymorphism significantly increased the risk of AS in Caucasians and decreased the risk of AS in mixed populations. Besides, rs361525 and rs1800630 polymorphisms conferred to an elevated risk of AS, and rs1799724 conferred to a reduced risk of AS in Asians. Conclusions: This study suggests that rs1800629 polymorphism is associated with an increased AS risk in Caucasians, rs361525 and rs1800630 polymorphisms are linked to an elevated AS susceptibility in Asians.