ERAP1 genetic variations associated with HLA-B27 interaction and disease severity of syndesmophytes formation in Taiwanese ankylosing spondylitis
1 Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, No. 5, Fu-Shin St. Kwei-Shan, Tao-Yuan, 33375 Taiwan
2 Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, No. 5, Fu-Shin St. Kwei-Shan, Tao-Yuan, 33375 Taiwan
3 Clinical Informatics and Medical Statistics Research Center, Chang Gung University, 259 Wenhua 1st Road, Kwei-Shan, Tao-Yuan, 33375 Taiwan
4 Department of Laboratory Medicine, Chang-Gung Memorial Hospital and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, No. 5, Fu-Shin St. Kwei-Shan, Tao-Yuan, 33375 Taiwan
5 Deptartment of Veterinary and Biomedical Sciences, 235B Animal Science/Vet. Med. Bldg., University of Minnesota,1988 Fitch Avenue, St. Paul, MN 55108, USA
Arthritis Research & Therapy 2012, 14:R125 doi:10.1186/ar3855Published: 25 May 2012
Ankylosing spondylitis (AS) is a familial, heritable disease specified by syndesmophyte formation leading to an ankylosed spine. Endoplasmic reticulum aminopeptidase 1 (ERAP1) genetic variations have been widely proved to be associated with AS in several ethnic populations. The aim of this study was to investigate whether ERAP1 single nucleotide polymorphisms (SNPs) are associated with AS susceptibility and disease severity in Taiwanese.
Four ERAP1 SNPs (rs27037, rs27980, rs27044 and rs30187) were genotyped in 797 Taiwanese AS patients and 1,150 healthy controls. Distributions of genotype and alleles were compared between AS patients and healthy controls, and among AS patients stratified by clinical parameters.
The SNP rs27037T allele appeared to be a risk factor for AS susceptibility (P = 5.5 × 10-5, OR 1.30, 95% CI: 1.15 to 1.48; GT+TT vs. GG P = 9.3 × 10-5, OR 1.49, 95% CI: 1.22 to 1.82). In addition, the coding SNP (cSNP) rs27044G allele (P = 1.5 × 10-4, OR 1.28, 95% CI: 1.13 to 1.46; CG+GG vs. CC, P = 1.7 × 10-3, OR 1.44, 95% CI: 1.15 to 1.81) and the cSNP rs30187T allele (P = 1.7 × 10-3, OR 1.23, 95% CI: 1.08 to 1.40; CT+TT vs. CC P = 6.1 × 10-3, OR 1.38, 95% CI: 1.10 to 1.74) were predisposing factors for AS. Notably, the rs27044G allele carriers (CG+GG vs. CC, P = 0.015, OR 1.59, 95% CI: 1.33 to 2.30) and rs30187T allele carriers (CT+TT vs. CC, P = 0.011, OR 1.63, 95% CI: 1.12 to 2.38) were susceptible to syndesmophyte formation in AS patients. Furthermore, two cSNPs (rs27044 and rs30187) strongly associated with HLA-B27 positivity in AS patients. Finally, the ERAP1 SNP haplotype TCG (rs27037T/rs27980C/rs27044G) is a major risk factor for AS (adjusted P <0.00001, OR 1.38, 95% CI: 1.12 to 1.58) in Taiwanese.
This study provides the first evidence of ERAP1 SNPs involving syndesmophyte formation. The interactions between ERAP1 SNPs and HLA-B27 play critical roles in pMHC I pathway processing contributing to the pathogenesis of AS in multiple populations.