ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms by Onouchi Yoshihiro, Gunji Tomohiko, Burns Jane C, Shimizu Chisato, Newburger Jane W, Yashiro Mayumi, Nakamura Yoshikazu, Yanagawa Hiroshi, Wakui Keiko, Fukushima Yoshimitsu, Kishi Fumio, Hamamoto Kunihiro, Terai Masaru, Sato Yoshitake, Ouchi Kazunobu, Saji Tsutomu, Nariai Akiyoshi, Kaburagi Yoichi, Yoshikawa Tetsushi, Suzuki Kyoko, Tanaka Takeo, Nagai Toshiro, Cho Hideo, Fujino Akihiro, Sekine Akihiro, Nakamichi Reiichiro, Tsunoda Tatsuhiko, Kawasaki Tomisaku, Nakamura Yusuke, Hata Akira in Nature genetics (2008). PubMed

Abstract

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.

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