The MHC2TA-168A/G polymorphism and risk for rheumatoid arthritis: a meta-analysis of 6861 patients and 9270 controls reveals no evidence for association

Background: An association between major histocompatibility complex (MHC) genes, particularly those within the class II HLA region, and rheumatoid arthritis (RA) is well established, and accounts for an estimated 30% of the genetic component in RA. The MHC class II transactivator gene (MHC2TA) on chromosome 16p13 has recently emerged as the most important transcription factor regulating genes required for class II MHC-restricted antigen presentation. Previous studies of a promoter region polymorphism (-168A/G, rs3087456) in the MHC2TA gene and RA have yielded conflicting results. Objective: To assess the association of the MHC2TA -168A/G polymorphism (rs3087456) and risk for RA by meta-analysis. Methods: Meta-analysis was performed for 6861 patients with RA and 9270 controls from 10 case -control studies. Odds ratios (ORs) and 95% confidence intervals (Cls) were calculated for each study. Summary ORs and 95% Cls were calculated for random effects models. Results: No effect was observed for the G risk allele (OR 1.02, 95% Cl 0.93 to 1.12, p = 0.70) or the GG risk genotype (OR 1.14, 95% Cl 0.95 to 1.36, p = 0.16). Conclusions: Our results indicate that the MHC2TA -168A/G polymorphism (rs3087456) is not associated with RA yet underscore the importance of including shared epitope allele carrier status, secondary phenotypes and more complete characterisation of MHC2TA variation in future studies.