Lack of association of TNF-α promoter polymorphisms with ankylosing spondylitis: a meta-analysis

Objectives. Genetic factors, in addition to the HLA-B27, could play a role in the pathogenesis of AS. TNF-alpha promoter polymorphisms have been reported to be associated with AS susceptibility, but the results of these previous studies have been inconsistent. The aim of this study was to explore whether TNF-alpha promoter polymorphisms confer susceptibility to AS. Methods. We conducted a random effect meta-analysis on the association of the A/A genotype (the recessive effect), the A/A+A/G genotype (the dominant effect) and the A allele of the TNF-alpha -308 and -238 polymorphisms with AS. Results. Eight studies, consisting of seven European studies and one Latin American study, were included in this meta-analysis. Any association between AS and the TNF-alpha -308 A allele was not found [odds ratio (OR) = 0.911; 95% CI 0.512, 1.286; P=0.636; I-2=73.8]. There was also no association of the TNF-alpha -308 AA and AA+AG genotypes with AS. Meta-analysis of the TNF-alpha -238 polymorphisms showed no association with AS (OR for A allele=0.930; 95% CI 0.498, 1.737; P=0.821; I-2=71.6). Subgroup analysis by ethnicity and HLA-B27 positivity did not change the results for the association of the TNF-alpha -308 and -238 polymorphisms with AS. Conclusions. This meta-analysis including 2247 subjects has shown that there is a lack of association of the TNF-alpha -308 A/G and -238 A/G polymorphisms with AS.