ERAP1 is associated with ankylosing spondylitis in Han Chinese.
ABSTRACT Genetic components play important roles in the incidence and development of ankylosing spondylitis (AS). Aminopeptidase regulator of tumor necrosis factor receptor shedding 1 (ERAP1) was recently found to be associated with AS in North American and British cohorts. We evaluated whether ERAP1 is associated with AS in a Chinese Han population.
A sample of 50 patients and 50 healthy controls was recruited for preliminary screening for informative single-nucleotide polymorphisms (SNP). Then 6 SNP of suggestive significance in the initial screening were followed up in a large sample of 471 patients with AS and 456 ethnically matched controls. Diagnosis of AS followed the 1984 modified New York criteria. Linkage disequilibrium coefficient (D' and r(2)) and haplotypes were estimated by Haploview. Result. Two SNP (rs27434, p = 0.00039, and rs27529, p = 0.0083) in ERAP1 other than that reported previously were found to be significantly associated with AS. Haplotype analysis using 5 SNP within 1 linkage disequilibrium block identified 2 risk haplotypes (GATGT and GACGT) and 1 protective haplotype (GGTGT) for AS.
Our study demonstrated that 2 novel SNP in ERAP1 were associated with AS in the Han Chinese population, suggesting that ERAP1 might confer genetic risk for AS in Han Chinese through the common mechanism shared by different populations, although the AS-associated SNP in ERAP1 might be population-specific.
- SourceAvailable from: Su-Wei Chang[show abstract] [hide abstract]
ABSTRACT: 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.Arthritis research & therapy 05/2012; 14(3):R125. · 4.27 Impact Factor