The association between tumor necrosis factor alpha promoter polymorphisms and ankylosing spondylitis: A meta-analysis

Background: Studies investigating the association between tumor necrosis factor (TNF)-alpha promoter polymorphisms and ankylosing spondylitis have reported conflicting results. We here performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. Methods: We performed a systematic search of the National Library of Medline and Embase databases before January 2013. This meta-analysis included 14 case-control studies, which included 1607 ankylosing spondylitis cases and 1910 controls. Results: The combined results based on all studies showed that ankylosing spondylitis cases had a significantly lower frequency of -308GA [OR (codominant model) = 0.81, 95% CI = 0.66, 0.99, P = 0.04], -857CT [OR (codominant model) = 0.55, 95% CI = 0.32, 0.94, P = 0.03], -863AA [OR (codominant model) = 0.11, 95% CI = 0.01, 0.94, P = 0.04], -863CA [OR (codominant model) = 0.32, 95% CI = 0.18, 0.58, P < 0.001], and -1031TC [OR (codominant model) = 0.44, 95% CI = 0.25, 0.77, P = 0.004] genotype. However, ankylosing spondylitis cases had a significantly higher frequency of -238AA [OR (recessive model) = 7.43, 95% CI = 3.66, 15.05, P < 0.001] and -850TT [OR (recessive model) = 2.49, 95% CI = 1.16, 5.34, P = 0.02; OR (codominant model) = 2.83, 95% CI = 1.28, 6.25, P = 0.01] genotype. In the subgroup analysis by race, we found that ankylosing spondylitis cases had a significantly higher frequency of -238AA [OR (recessive model) = 7.43,95% CI = 3.66, 15.05, P < 0.001] genotype in Caucasians and lower frequency of -857CT [OR (codominant model) = 0.53, 95% Cl = 0.30, 0.94, P = 0.03] in Asians. Conclusions: Our meta-analysis suggests that TNF-alpha promoter polymorphisms at positions -238, -308, -850, -857, -863 and -1031 could have a small influence on ankylosing spondylitis susceptibility. But there is a lack of association of the TNF-alpha-376G/A and -646G/A polymorphisms with ankylosing spondylitis. (c) 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.