ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms

被引：356

作者：

Onouchi Y. ^{[1
,26
]}

Gunji T. ^{[1
,2
,26
]}

Burns J.C. ^{[3
,4
]}

Shimizu C. ^{[3
,4
]}

Newburger J.W. ^{[5
]}

Yashiro M. ^{[6
]}

Nakamura Y. ^{[6
]}

Yanagawa H. ^{[7
]}

Wakui K. ^{[8
]}

Fukushima Y. ^{[8
]}

Kishi F. ^{[9
]}

Hamamoto K. ^{[10
]}

Terai M. ^{[11
]}

Sato Y. ^{[12
]}

Ouchi K. ^{[13
]}

Saji T. ^{[14
]}

Nariai A. ^{[15
]}

Kaburagi Y. ^{[15
,27
]}

Yoshikawa T. ^{[16
]}

Suzuki K. ^{[17
]}

Tanaka T. ^{[18
]}

Nagai T. ^{[19
]}

Cho H. ^{[20
]}

Fujino A. ^{[21
]}

Sekine A. ^{[22
,26
]}

Nakamichi R. ^{[23
,26
]}

Tsunoda T. ^{[23
,26
]}

Kawasaki T. ^{[24
]}

Nakamura Y. ^{[6
]}

Hata A. ^{[1
,26
]}

机构：

[1] Laboratory for Gastrointestinal Diseases, SNP Research Center, RIKEN, Yokohama, Kanagawa

[2] Department of Hard Tissue Engineering, Graduate School Tokyo Medical and Dental University

[3] Department of Pediatrics, University of California San Diego, School of Medicine, San Diego, CA

[4] Rady Children's Hospital, San Diego

[5] Department of Cardiology, Boston Children's Hospital, Boston

[6] Department of Public Health, Jichi Medical School, Tochigi 329-0498, Minamikawachi

[7] Saitama Prefectural University, Koshigaya

[8] Department of Preventive Medicine, Shinshu University School of Medicine

[9] Department of Molecular Genetics, Kawasaki Medical School, Kurashiki

[10] Department of Pediatrics, Fukuoka University School of Medicine, Fukuoka

[11] Department of Pediatrics, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo

[12] Department of Pediatrics, Fuji Heavy Industries Ltd., Health Insurance Society General Ohta Hospital, Ohta

[13] Department of Pediatrics, Kawasaki Medical School, Kurashiki

[14] Department of Pediatrics, Toho University School of Medicine

[15] Department of Pediatrics, Yokohama Minami Kyousai Hospital, Yokohama, 236-0037, Kanagawa

[16] Department of Pediatrics, Fujita Health University, Toyoake

[17] Department of Pediatrics, Toyokawa Citizen's Hospital, Toyokawa

[18] Department of Pediatrics, National Hospital Organization Kure Medical Center, Kure

[19] Department of Pediatrics, Dokkyo Medical University, Koshigaya Hospital, Koshigaya

[20] Department of Pediatrics, Kawasaki Municipal Hospital

[21] Department of Surgery, Keio University School of Medicine

[22] Laboratory for Genotyping, SNP Research Center, RIKEN, Yokohama

[23] Laboratory for Medical Informatics, SNP Research Center, RIKEN, Yokohama

[24] Japan Kawasaki Disease Research Center

[25] Laboratory for Molecular Medicine, Institute of Medical Science, University of Tokyo

[26] SNP Research Center, RIKEN, Yokohama

[27] Department of Pediatrics, National Hospital Organization Yokohama Medical Center, Yokohama

来源：

Nature Genetics | 2008年 / 40卷 / 1期

基金：

日本学术振兴会; 美国国家卫生研究院;

关键词：

D O I：

10.1038/ng.2007.59

中图分类号：

学科分类号：

摘要：

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. © 2008 Nature Publishing Group.

引用

页码：35 / 42

页数：7

共 41 条

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