ERAP1 polymorphisms and haplotypes are associated with ankylosing spondylitis susceptibility and functional severity in a Spanish population.
OBJECTIVES The aim of this study was to assess the involvement of the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene in AS susceptibility and functional severity in a Spanish population. METHODS Eight single nucleotide polymorphisms (SNPs) spanning the ERAP1 gene were genotyped by allele-specific fluorescent PCR in 300 AS Spanish patients and 300 spondylarthritis-free controls. The influence of the ERAP1 SNPs on the functional severity of AS was analysed with the BASFI corrected for disease duration. Association analyses with AS susceptibility and functional severity were performed. RESULTS Significant ERAP1 single marker association with AS susceptibility was found for five SNPs, namely rs30187 (allele T: P = 0.035), rs17482078 (allele C: P = 0.030), rs2287987 (allele T: P = 0.028), rs26653 (allele C: P = 0.041) and rs10050860 (allele C: P = 0.018). Three of the associated SNPs (rs17482078, rs2287987 and rs10050860) were in strong linkage disequilibrium. After imputing genotypes with the HapMap CEU data as reference, the strongest association was with rs41135 (P = 0.0046) in the 5'-upstream region of ERAP1. In addition, the SNP rs17481856 was found to be a risk factor for functional severity in AS and a borderline trend was observed for rs27044. CONCLUSIONS These results suggest that the ERAP1 gene is associated with genetic predisposition to AS and influences the functional severity of the disease in a Spanish population.