ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms
ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms
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DOI：
10.1038/ng.2007.59
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发表时间：
2008-01-01
期刊：
影响因子：
30.8
通讯作者：
Hata, Akira
中科院分区：
文献类型：
--
作者：
Onouchi, Yoshihiro;Gunji, Tomohiko;Hata, Akira
川崎病是一种病因不明的小儿系统性血管炎，怀疑有遗传影响。我们在染色体 19q13.2 上的肌醇 1,4,5-三磷酸 3-激酶 C (ITPKC) 基因中发现了一个功能性 SNP (itpkc_3)，该基因与日本和美国儿童的川崎病易感性以及冠状动脉病变风险增加显着相关。转染实验表明，itpkc_3 的 C 等位基因降低了 ITPKC mRNA 的剪接效率。 ITPKC 通过 Ca2+/NFAT 信号通路充当 T 细胞激活的负调节因子，C 等位基因可能导致川崎病的免疫高反应性。这一发现为川崎病免疫激活机制提供了新的见解，并强调了激活的 T 细胞在这种血管炎发病机制中的重要性。
Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children. Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis.