ERAP1 genetic variations associated with HLA-B27 interaction and disease severity of syndesmophytes formation in Taiwanese ankylosing spondylitisReportar como inadecuado

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Arthritis Research and Therapy

, 14:R125

First Online: 25 May 2012Received: 01 November 2011Revised: 08 March 2012Accepted: 25 May 2012


IntroductionAnkylosing 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.

MethodsFour 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.

ResultsThe SNP rs27037T allele appeared to be a risk factor for AS susceptibility P = 5.5 × 10, OR 1.30, 95% CI: 1.15 to 1.48; GT+TT vs. GG P = 9.3 × 10, OR 1.49, 95% CI: 1.22 to 1.82. In addition, the coding SNP cSNP rs27044G allele P = 1.5 × 10, OR 1.28, 95% CI: 1.13 to 1.46; CG+GG vs. CC, P = 1.7 × 10, OR 1.44, 95% CI: 1.15 to 1.81 and the cSNP rs30187T allele P = 1.7 × 10, OR 1.23, 95% CI: 1.08 to 1.40; CT+TT vs. CC P = 6.1 × 10, 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.

ConclusionsThis 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.

AbbreviationsASankylosing spondylitis

CMHCochran -Mantel -Haenszel

DCsdendritic cells

DMdiabetes mellitus

ERendoplasmic reticulum

ERAP1endoplasmic reticulum aminopeptidase 1

FHCfree heavy chain

GWASgenome wide association studies


LDlinkage disequilibrium

LMP2large multifunctional peptidase 2

MHCmajor histocompatibility complex

mSASSSmodified Stoke-s Ankylosing Spondylitis Spinal Score

ORsodds ratios

RArheumatoid arthritis

SLEsystemic lupus erythematous

SNPsingle nucleotide polymorphism

TCRT cell receptor

TNFR1tumor necrosis factor receptor 1

UPRsunfolded protein responses

Electronic supplementary materialThe online version of this article doi:10.1186-ar3855 contains supplementary material, which is available to authorized users.

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Autor: Chin-Man Wang - Huei-Huang Ho - Su-Wei Chang - Yeong-Jian Jan Wu - Jing-Chi Lin - Pi-Yueh Chang - Jianming Wu - Ji-Yih Ch


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