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Arthritis Res Ther. 2012; 14(3): R125.
Published online May 25, 2012. doi:  10.1186/ar3855
PMCID: PMC3446506
ERAP1 genetic variations associated with HLA-B27 interaction and disease severity of syndesmophytes formation in Taiwanese ankylosing spondylitis
Chin-Man Wang,1 Huei-Huang Ho,2 Su-Wei Chang,3 Yeong-Jian Jan Wu,2 Jing-Chi Lin,2 Pi-Yueh Chang,4 Jianming Wu,5 and Ji-Yih Chencorresponding author2
1Department 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
2Department 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
3Clinical Informatics and Medical Statistics Research Center, Chang Gung University, 259 Wenhua 1st Road, Kwei-Shan, Tao-Yuan, 33375 Taiwan
4Department 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
5Deptartment of Veterinary and Biomedical Sciences, 235B Animal Science/Vet. Med. Bldg., University of Minnesota,1988 Fitch Avenue, St. Paul, MN 55108, USA
corresponding authorCorresponding author.
Chin-Man Wang: cmw1314/at/adm.cgmh.org.tw; Huei-Huang Ho: HueiHuang0731/at/yahoo.com.tw; Su-Wei Chang: shwchang/at/mail.cgu.edu.tw; Yeong-Jian Jan Wu: yjwu1962/at/adm.cgmh.org.tw; Jing-Chi Lin: jingchilin/at/gmail.com; Pi-Yueh Chang: changpy/at/cgmh.org.tw; Jianming Wu: jmwu/at/umn.edu; Ji-Yih Chen: jychen31/at/adm.cgmh.org.tw
Received November 1, 2011; Revised March 8, 2012; Accepted May 25, 2012.
Abstract
Introduction
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.
Methods
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.
Results
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.
Conclusions
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.
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