Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese
Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese
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DOI：
10.1136/ard.2008.104315
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发表时间：
2010-02-01
影响因子：
27.4
通讯作者：
Momohara, S.
中科院分区：
文献类型：
--
作者：
Nishimoto, K.;Kochi, Y.;Momohara, S.
目的：本研究的主要目的是调查TRAF 1-C5多态性与日本人群中RA和系统性红斑狼疮（SLE）易感性的相关性，TRAF 1-C5是一种新发现的白种人类风湿关节炎（RA）风险位点。方法：采用多中心关联研究方法，对4个RA病例对照系列（4397例和2857例对照）和3个SLE病例对照系列（591例和2199例共同对照）进行分析。使用TaqMan基因分型试验对两个单核苷酸多态性（SNP）进行基因分型，这两个SNP在以前的高加索人研究中显示出最好的关联证据。结果：RA组和对照组TRAF 1和C5基因的等位基因频率差异有统计学意义（合并优势比= 1.09），而SLE组和对照组TRAF 1和C5基因的等位基因频率差异无统计学意义（P> 0.05）。有趣的是，等位基因rs3761847 A和rs 10818488 G在本研究中增加了RA的风险，而在原始研究中降低了风险。rs 10818488危险等位基因携带者和非携带者在佛波酯刺激的淋巴母细胞系中TRAF 1的表达水平存在显著差异（p = 0.04）。结论：TRAF 1-C5基因座与RA易感性在日本人群中存在中度相关性，而与SLE无显著相关性。TRAF 1基因型对RA的表达有显著的正向影响，这可能支持TRAF 1与RA的遗传相关性。
Objective: The primary aim of this study was to investigate the association of polymorphisms of TRAF1-C5, a newly identified rheumatoid arthritis (RA) risk locus in Caucasians, with susceptibility to RA and systemic lupus erythematosus (SLE) in Japanese populations. Gene expression levels of TRAF1 and C5 to assess the functional significance of genotypes were also analysed.Methods: A multicentre association study consisting of 4 RA case-control series (4397 cases and 2857 controls) and 3 SLE case-control series (591 cases and 2199 shared controls) was conducted. Genotyping was performed using TaqMan genotyping assay for two single nucleotide polymorphisms (SNPs) that showed the best evidence of association in the previous Caucasian studies. Quantifications of TRAF1 and C5 expression were performed with TaqMan expression assay.Results: Significant differences in allele frequency for both SNPs were observed between RA and control subjects (combined odds ratio = 1.09), while no significant difference was detected between patients with SLE and controls. Interestingly, alleles rs3761847 A and rs10818488 G had increased the risk for RA in the present study, while they decreased the risk in the original studies. A significant difference was found between risk allele carriers and non-carriers of rs10818488 for the expression level of TRAF1 in phorbol myristate acetate-stimulated lymphoblastoid cell lines (p = 0.04).Conclusion: Association of TRAF1-C5 locus with RA susceptibility was detected in the Japanese populations with modest magnitude, while no significant association was observed for SLE. Significant positive effect of genotype on the expression of TRAF1 might support the genetic association between TRAF1 and RA.