The Association of a Nonsynonymous Single-Nucleotide Polymorphism in TNFAIP3 With Systemic Lupus Erythematosus and Rheumatoid Arthritis in the Japanese Population
The Association of a Nonsynonymous Single-Nucleotide Polymorphism in TNFAIP3 With Systemic Lupus Erythematosus and Rheumatoid Arthritis in the Japanese Population
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DOI：
10.1002/art.27190
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发表时间：
2010-02-01
影响因子：
--
通讯作者：
Yamamoto, Kazuhiko
中科院分区：
文献类型：
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作者：
Shimane, Kenichi;Kochi, Yuta;Yamamoto, Kazuhiko
Objective.全基因组关联（GWA）研究系统性红斑狼疮（SLE）和类风湿性关节炎（RA）在高加索人群中已经独立地确定了风险变异的肿瘤坏死因子α（TNF α）诱导蛋白3基因（TNFAIP 3），这是至关重要的调节TNF介导的信号和Toll样受体信号。本研究的目的是评估TNFAIP 3在日本受试者中SLE和RA发展中的作用。我们从先前的GWA研究中选择了2个单核苷酸多态性（SNPs）。Rs 2230926是TNFAIP 3中的非同义SNP，与SLE相关，而rs 10499194是与RA相关的基因间SNP。然后，我们使用日本受试者进行了2组独立的SLE病例对照比较（717例患者和1，362例对照受试者）和3组RA病例对照比较（3，446例患者和2，344例对照受试者）。我们使用TaqMan分析对SNP进行基因分型。我们观察到rs 2230926与日本人群SLE和RA风险增加之间存在显著相关性（SLE，比值比[OR] 1.92，95%置信区间[95% CI] 1.53-2.41，P = 1.9 x 10（-8）; RA，OR 1.35，95% CI 1.18-1.56，P = 2.6 x 10（-5））。基因间SNP rs 10499194也与SLE和RA相关，而白种人RA的危险等位基因在我们人群中对疾病具有保护作用。我们证明了TNFAIP 3的非同义变异与日本人群中SLE和RA的风险之间存在显著相关性。TNFAIP 3与STAT 4和IRF 5类似，可能是白人和日本人群共同的SLE和RA的常见遗传风险因素。
Objective. Genome-wide association (GWA) studies in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Caucasian populations have independently identified risk variants in and near the tumor necrosis factor alpha (TNF alpha)-induced protein 3 gene (TNFAIP3), which is crucial for the regulation of TNF-mediated signaling and Toll-like receptor signaling. The aim of this study was to assess the role of TNFAIP3 in the development of SLE and RA in Japanese subjects.Methods. We selected 2 single-nucleotide polymorphisms (SNPs) from previous GWA studies. Rs2230926 is a nonsynonymous SNP in TNFAIP3 and is associated with SLE, while rs10499194 is an intergenic SNP associated with RA. We then performed 2 independent sets of SLE case-control comparisons (717 patients and 1,362 control subjects) and 3 sets of RA case-control comparisons (3,446 patients and 2,344 control subjects) using Japanese subjects. We genotyped SNPs using TaqMan assays.Results. We observed a significant association between rs2230926 and an increased risk of SLE and RA in the Japanese population (for SLE, odds ratio [OR] 1.92, 95% confidence interval [95% CI] 1.53-2.41, P = 1.9 x 10(-8); for RA, OR 1.35, 95% CI 1.18-1.56, P = 2.6 x 10(-5)). The intergenic SNP rs10499194 was also associated with SLE and RA, while the risk allele for RA in Caucasians was protective against the diseases in our population.Conclusion. We demonstrated a significant association between the nonsynonymous variant in TNFAIP3 and the risk for SLE and RA in the Japanese population. TNFAIP3, similar to STAT4 and IRF5, may be a common genetic risk factor for SLE and RA that is shared between the Caucasian and Japanese populations.