Identification of novel susceptibility Loci for kawasaki disease in a Han chinese population by a genome-wide association study.
Identification of novel susceptibility Loci for kawasaki disease in a Han chinese population by a genome-wide association study.
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DOI：
10.1371/journal.pone.0016853
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发表时间：
2011-02-04
期刊：
影响因子：
3.7
通讯作者：
Wu JY
中科院分区：
文献类型：
--
作者：
Tsai FJ;Lee YC;Chang JS;Huang LM;Huang FY;Chiu NC;Chen MR;Chi H;Lee YJ;Chang LC;Liu YM;Wang HH;Chen CH;Chen YT;Wu JY
川崎病（KD）是一种主要影响婴幼儿的急性全身性血管炎综合征。其病因不明；然而，流行病学研究结果表明，遗传易感性是疾病易感性的基础。台湾的KD发病率位居世界第三，仅次于日本和韩国。为了研究可能使个体易患KD的新机制，我们在居住在台湾的汉族人群中进行了250例KD患者和446例对照的全基因组关联研究（GWAS），并在208例和366例对照的独立汉族队列中进一步验证了我们的发现。在联合分析中检测到的最强烈相关的单核苷酸多态性（snp）对应于三个新的位点。在这些与帕金森病相关的snp中，有3个与COPB2（包膜蛋白复合物β -2亚基）基因接近：rs1873668 （p = 9.52×10−5）、rs4243399 （p = 9.93×10−5）和rs16849083 （p = 9.93×10−5）。我们还在ERAP1（内质网氨基肽酶1）基因的内含子区域发现了一个SNP （rs149481, pbest = 4.61×10−5）。6个snp （rs17113284、rs8005468、rs10129255、rs2007467、rs10150241和rs12590667）聚集在含有免疫球蛋白重链可变区基因的区域，pbest值在2.08×10−5和8.93×10−6之间。这是首次在汉族人群中进行KD GWAS。我们发现的新的KD候选者与T细胞受体信号传导、促炎细胞因子的调节以及抗体介导的免疫反应有关。这些发现可能有助于更好地了解KD的潜在分子发病机制。
Kawasaki disease (KD) is an acute systemic vasculitis syndrome that primarily affects infants and young children. Its etiology is unknown; however, epidemiological findings suggest that genetic predisposition underlies disease susceptibility. Taiwan has the third-highest incidence of KD in the world, after Japan and Korea. To investigate novel mechanisms that might predispose individuals to KD, we conducted a genome-wide association study (GWAS) in 250 KD patients and 446 controls in a Han Chinese population residing in Taiwan, and further validated our findings in an independent Han Chinese cohort of 208 cases and 366 controls. The most strongly associated single-nucleotide polymorphisms (SNPs) detected in the joint analysis corresponded to three novel loci. Among these KD-associated SNPs three were close to the COPB2 (coatomer protein complex beta-2 subunit) gene: rs1873668 (p = 9.52×10−5), rs4243399 (p = 9.93×10−5), and rs16849083 (p = 9.93×10−5). We also identified a SNP in the intronic region of the ERAP1 (endoplasmic reticulum amino peptidase 1) gene (rs149481, pbest = 4.61×10−5). Six SNPs (rs17113284, rs8005468, rs10129255, rs2007467, rs10150241, and rs12590667) clustered in an area containing immunoglobulin heavy chain variable regions genes, with pbest-values between 2.08×10−5 and 8.93×10−6, were also identified. This is the first KD GWAS performed in a Han Chinese population. The novel KD candidates we identified have been implicated in T cell receptor signaling, regulation of proinflammatory cytokines, as well as antibody-mediated immune responses. These findings may lead to a better understanding of the underlying molecular pathogenesis of KD.
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影响因子：
6.4
作者：
Rowley, AH;Baker, SC;Crawford, SE
通讯作者：
Crawford, SE
影响因子：
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作者：
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International Kawasaki Disease Genetics Consortium
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作者：
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