Association of ERAP1, but Not IL23R, With Ankylosing Spondylitis in a Han Chinese Population
Association of ERAP1, but Not IL23R, With Ankylosing Spondylitis in a Han Chinese Population
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DOI：
10.1002/art.24933
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发表时间：
2009-11-01
影响因子：
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通讯作者：
Xu, Huji
中科院分区：
文献类型：
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作者：
Davidson, Stuart I.;Wu, Xin;Xu, Huji
目标。最近一项全基因组关联研究的结果表明，ERAP1和IL23R与北美和英国高加索人群的强直性脊柱炎（AS）有关。基于这些发现，我们开展了当前的研究，以调查覆盖ERAP1和IL23R基因的单核苷酸多态性（snp）是否与中国汉族人群的AS相关。我们对来自上海和南京的汉族AS患者（n = 527）和对照组（n = 945）进行了病例对照研究。所有患者均符合修改后的纽约AS标准。使用Sequenom iPlex平台对病例和对照组的21个IL23R标签snp和38个ERAP1标签snp进行基因分型。统计学分析采用Cochran-Armitage检验。ERAP1中的多个snp与AS显著相关（rs27980, P = 0.0048; rs7711564, P = 0.0081）。然而，没有观察到IL23R和AS之间的关联（对于所有snp， P >.1）。IL23R的非同义SNP rs11209026，被广泛认为是欧洲人IL23R的主要as相关SNP，在中国人中没有发现多态性。我们的研究结果表明，ERAP1基因多态性与汉族AS相关，提示中国和高加索人群AS存在共同的致病机制，而IL23R基因与中国AS不相关，提示中国和高加索人群AS的发病机制存在差异。这可能是由于IL23R中的非同义SNP rs11209026在中国患者中不存在多态性，进一步证明rs11209026是该基因中与AS（以及可能的炎症性肠病和牛皮癣）相关的关键多态性。
Objective. The results of a recent genome-wide association study have shown that ERAP1 and IL23R are associated with ankylosing spondylitis (AS) in Caucasian populations from North America and the UK. Based on these findings, we undertook the current study to investigate whether single-nucleotide polymorphisms (SNPs) covering the genes ERAP1 and IL23R are associated with AS in a Han Chinese population.Methods. A case-control study was performed in Han Chinese patients with AS (n = 527) and controls (n = 945) from Shanghai and Nanjing. All patients met the modified New York criteria for AS. The Sequenom iPlex platform was used to genotype cases and controls for 21 tag SNPs covering IL23R and 38 tag SNPs covering ERAP1. Statistical analysis was performed using the Cochran-Armitage test for trend.Results. Multiple SNPs in ERAP1 were significantly associated with AS (for rs27980, P = 0.0048; for rs7711564, P = 0.0081). However, no association was observed between IL23R and AS (for all SNPs, P > 0.1). The nonsynonymous SNP in IL23R, rs11209026, widely thought to be the primary AS-associated SNP in IL23R in Europeans, was found not to be polymorphic in Chinese.Conclusion. Our results demonstrate that genetic polymorphisms in ERAP1 are associated with AS in Han Chinese, suggesting a common pathogenic mechanism for the disease in Chinese and Caucasian populations, and that IL23R is not associated with AS in Chinese, indicating a difference in the mechanism of disease pathogenesis between Chinese and Caucasian populations. This may result from the fact that rs11209026, the nonsynonymous SNP in IL23R, is not polymorphic in Chinese patients, providing further evidence that rs11209026 is the key polymorphism associated with AS (and likely inflammatory bowel disease and psoriasis) in this gene.