Laboratory for Cardiovascular diseases, Center for Genomic Medicine RIKEN, Yokohama 230-0045, Japan.
Hum Mol Genet. 2010 Jul 15;19(14):2898-906. doi: 10.1093/hmg/ddq176. Epub 2010 Apr 27.
Kawasaki disease (KD; OMIM 611775) is an acute vasculitis syndrome which predominantly affects small- and medium-sized arteries of infants and children. Epidemiological data suggest that host genetics underlie the disease pathogenesis. Here we report that multiple variants in the caspase-3 gene (CASP3) that are in linkage disequilibrium confer susceptibility to KD in both Japanese and US subjects of European ancestry. We found that a G to A substitution of one commonly associated SNP located in the 5' untranslated region of CASP3 (rs72689236; P = 4.2 x 10(-8) in the Japanese and P = 3.7 x 10(-3) in the European Americans) abolished binding of nuclear factor of activated T cells to the DNA sequence surrounding the SNP. Our findings suggest that altered CASP3 expression in immune effecter cells influences susceptibility to KD.
川崎病（KD；OMIM 611775）是一种主要影响婴幼儿中小动脉的急性血管炎综合征。流行病学数据表明，宿主遗传学是疾病发病机制的基础。在这里，我们报告称，位于半胱氨酸天冬氨酸蛋白酶 3（CASP3）基因中的多个与连锁不平衡相关的变体可使日本和美国欧洲裔人群易患 KD。我们发现，位于 CASP3 5'非翻译区的一个常见相关 SNP（rs72689236；日本人中的 P = 4.2×10(-8)，欧洲裔美国人中的 P = 3.7×10(-3)）的 G 到 A 取代消除了核因子活化 T 细胞与 SNP 周围 DNA 序列的结合。我们的研究结果表明，免疫效应细胞中 CASP3 表达的改变影响了 KD 的易感性。
