Background Genetic research in axSpA is performed in patients with longstanding ankylosing spondylitis (AS). Early axial spondyloarthritis (axSpA) is a diverse patient group in which a minority of the patients have AS. Therefore, it is not known if recently identified genetic risk factors for AS are also risk factors for early axSpA.
Objectives To evaluate if ERAP1 and HLA-B*4001 are susceptibility factors for early axSpA.
Methods Patients with early axSpA meeting the ASAS classification criteria from the SPACE cohort (inclusion criteria: back pain for ≥3 months, ≤2 years, onset <45 years) and the DESIR cohort (inclusion criteria: inflammatory back pain for ≥3 months, ≤3 years, age <50) were typed for two well established AS genetic risk factors: ERAP1 SNPs rs30187 (susceptibility), rs17482078 (protective) and rs10050860 (neutral) and HLA-B*4001. Analysis of weaker AS risk factors was limited by sample size. For ERAP1, genotyped Dutch healthy controls (n=1085) and published French controls1 were used as controls. For HLA-B*4001 healthy blood bank donors from the Netherlands (n=5584) and France (n=10177) were used as controls.
Results In 486 DESIR patients (mean age 32.5 (SD 8.6); 50% male; 84% HLA-B27+; 18% X-SI+) and 144 SPACE patients (mean age 29.5 (SD 8); 51% male; 88% HLA-B27+; 24% X-SI+) ERAP1 SNP rs30187 was more common than in controls (OR 1.2, p=0.01 in meta-analysis; table 1). rs17482078 and rs10050860 were negatively associated with early axSpA (both 0.7 (0.6–0.9) p<0.01 in meta-analysis). Although both cohorts were sufficiently powered, HLA-B*4001 was not positively associated with early axSpA (OR 0.6 (0.4–0.9) in meta-analysis).
Conclusions ERAP1 rs30187 is a genetic risk factor for early axSpA. To our knowledge this is the first report of genetic risk factor research in early axSpA patients meeting the ASAS criteria. Larger cohorts are needed to study additional AS risk factors.
Kadi A, Izac B, Said-Nahal R, Leboime A, Van Praet L, de Vlam K, et al. Investigating the genetic association between ERAP1 and spondyloarthritis. Ann Rheum Dis. 2013;72(4):608–13.
Disclosure of Interest None declared