Association of STAT3 and TNFRSF1A with ankylosing spondylitis in Han Chinese

单核苷酸多态性 医学 强直性脊柱炎 SNP公司 逻辑回归 遗传关联 人口 遗传学 内科学 基因 基因型 生物 环境卫生
作者
Sean Davidson,Y. Liu,Patrick Danoy,Xin Wu,Gethin Thomas,Lei Jiang,Lingyun Sun,N. Wang,Junyong Han,Hedong Han,Peter M. Visscher,Matthew A. Brown,Huji Xu
出处
期刊:Annals of the Rheumatic Diseases [BMJ]
卷期号:70 (2): 289-292 被引量:101
标识
DOI:10.1136/ard.2010.133322
摘要

Objectives

Recent association studies by the Australo-Anglo-American Spondyloarthritis Consortium (TASC) in Caucasian European populations from Australia, North America and the UK have identified a number of genes as being associated with ankylosing spondylitis (AS). A candidate gene study in a Han Chinese population was performed based on these findings to identify associated genes in this population.

Methods

A case-control study was performed in a Han Chinese population of patients with AS (n=775) and controls (n=1587) from Shanghai and Nanjing. All patients met the modified New York criteria for AS. The cases and controls were genotyped for 115 single nucleotide polymorphisms (SNPs) tagging IL23R, ERAP1, STAT3, JAK2, TNFRSF1A and TRADD, as well as other confirmation SNPs from the TASC study, using the Sequenom iPlex and the ABI OpenArray platforms. Statistical analysis of genotyped SNPs was performed using the Cochran–Armitage test for trend and meta-analysis was performed using METAL. SNPs in AS-associated genes in this study were then imputed using MaCH, and association with AS tested by logistic regression.

Results

SNPs in TNFRSF1A (rs4149577, p=8.2×10−4), STAT3 (rs2293152, p=0.0015; rs1053005, p=0.017) and ERAP1 (rs27038, p=0.0091; rs27037, p=0.0092) were significantly associated with AS in Han Chinese. Association was also observed between AS and the intergenic region 2p15 (rs10865331, p=0.023). The lack of association between AS and IL23R in Han Chinese was confirmed (all SNPs p>0.1).

Conclusions

The study results demonstrate for the first time that genetic polymorphisms in STAT3, TNFRSF1A and 2p15 are associated with AS in Han Chinese, suggesting common pathogenic mechanisms for the disease in Chinese and Caucasian European populations. Furthermore, previous findings demonstrating that ERAP1, but not IL23R, is associated with AS in Chinese patients were confirmed.

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