Investigating the genetic association between ERAP1 and spondyloarthritis

Objective A robust association between polymorphisms in the non-major histocompatibility complex gene ERAP1 and ankylosing spondylitis (AS) in several populations was recently identified. The aim of the current study was to determine the level of association of ERAP1 polymorphisms with spondyloarthritis (SpA) in French/Belgian populations with particular attention to genotype–phenotype correlations. Methods We studied 734 independent SpA cases and 632 controls from two European cohorts. Five single-nucleotide polymorphisms (SNPs), rs27044, rs17482078, rs10050860, rs30187 and rs2287987 were genotyped, and case-control association analyses were carried using PLINK 1.07 software. Linkage disequilibrium and haplotypes were estimated with Haploview. Analysis was first carried out in SpA as a whole group, and then separately in AS and non-radiographic SpA (non-AS) patients. Results Consistent with previous studies conducted in AS, rs30187 was the most significantly associated SNP with SpA (p=0.008 in the French, and p=6.46×10 −4 in the Belgian cohorts). In the combined cohorts, this SNP was associated with both AS and non-AS (P combined = 3.9×10 −5 and P combined = 0.005, respectively). A similar trend was observed with other SNPs. 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). Conclusions This is the first study to show an association between several polymorphisms located in ERAP1 and SpA as a whole. Our findings demonstrate consistent association of the same SNPs and haplotypes with both AS and non-AS subtypes of SpA.