To characterize the alterations, as well as their mechanisms, induced in the HLA-B27-bound peptidome expressed in live cells by the natural ERAP1 polymorphisms predisposing to ankylosing spondylitis (AS): R528K and N575D/Q725R.
The rs17482078/rs10050860/rs30187-CCT haplotype was significantly associated with increased risk of SpA in both cohorts (P(combined)= 9.08×10(-4)), including AS and non-AS (P(combined)=6.16×10(-4) and P(combined)=0.049, respectively), whereas the -TTC haplotype was associated with reduced risk of SpA, including AS and non-AS (P(combined)=2.36×10(-7), P(combined)= 5.69×10(-6) and P(combined)= 2.13×10(-4), respectively).
Except in rs27434 (P = 0.23), the significant correlation between ERAP1 polymorphisms and AS susceptibility has been detected in rs27044 (OR 1.57, P < 0.001), rs17482078 (OR 1.271, P < 0.001), rs10050860 (OR 0.772, P = 0.006), rs30187 (OR 1.348, P < 0.001), rs2287987 (OR 0.746, P < 0.001) and rs27037 (OR 1.257, P = 0.001).
This meta-analysis shows that the rs27044, rs17482078, rs10050860, rs30187, and rs2287987 polymorphisms of ERAP1 are associated with the development of AS in Europeans.