Association between cytokine gene polymorphisms and ankylosing spondylitis susceptibility: a systematic review and meta-analysis

Purpose of the study The aim of this study was to perform a meta-analysis to derive precise estimation of the association of interleukin-23 receptor (IL-23R), IL-1 receptor 2 (IL-1R2), IL-12 beta (IL-12B), IL-10 and tumour necrosis factor (TNF)- polymorphisms with ankylosing spondylitis (AS) susceptibility. Study design A systematic literature search was conducted to identify the relevant studies. Pooled OR with 95% CI was calculated to assess the strength of the association in a fixed or random-effects model. Results A total of 13917 cases and 19849 controls in 43 eligible studies were included in the meta-analysis. Seventeen single-nucleotide polymorphisms (SNPs) in the abovementioned five cytokine genes were evaluated. The results indicate that the nine SNPs (rs11209026, rs1004819, rs10489629, rs11465804, rs1343151, rs11209032, rs1495965, rs7517847, rs2201841) of IL-23R are associated with AS susceptibility in all study subjects in the allelic model. Moreover, stratification by ethnicity identified a significant association between seven SNPs of IL-23R and AS susceptibility in Europeans and Americans, but not in Asians. In addition, the IL-10-819 C/T and TNF--857 C/T polymorphisms also confer susceptibility to AS, especially in Asian population. Conclusion The results suggested that the genetic susceptibility for AS is associated with the nine SNPs of IL-23R in overall population. In the subgroup analysis, significant associations were shown in European and American population, but not in Asian population. Our results also suggest that IL-10-819 C/T and TNF--857 C/T polymorphism might be associated with AS risk, especially in Asian population.