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

Yoshihiro Onouchi, Tomohiko Gunji, Jane C. Burns, Chisato Shimizu, Jane W. Newburger, Mayumi Yashiro, Yoshikazu Nakamura, Hiroshi Yanagawa, Keiko Wakui, Yoshimitsu Fukushima, Fumio Kishi, Kunihiro Hamamoto, Masaru Terai, Yoshitake Sato, Kazunobu Ouchi, Tsutomu Saji, Akiyoshi Nariai, Yoichi Kaburagi, Tetsushi Yoshikawa, Kyoko SuzukiTakeo Tanaka, Toshiro Nagai, Hideo Cho, Akihiro Fujino, Akihiro Sekine, Reiichiro Nakamichi, Tatsuhiko Tsunoda, Tomisaku Kawasaki, Yusuke Nakamura, Akira Hata

研究成果: Article査読

336 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)35-42
ページ数8
ジャーナルNature Genetics
40
1
DOI
出版ステータスPublished - 01-2008

All Science Journal Classification (ASJC) codes

  • 遺伝学

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