title: ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms.
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.
authors: Laboratory for Gastrointestinal Diseases, SNP Research Center, RIKEN, Yokohama, Kanagawa, 230-0045, Japan. onouchi@src.riken.jp
authors: Yoshihiro
authors: Y
authors: Onouchi
authors: Tomohiko
authors: T
authors: Gunji
authors: Jane C
authors: JC
authors: Burns
authors: Chisato
authors: C
authors: Shimizu
authors: Jane W
authors: JW
authors: Newburger
authors: Mayumi
authors: M
authors: Yashiro
authors: Yoshikazu
authors: Y
authors: Nakamura
authors: Hiroshi
authors: H
authors: Yanagawa
authors: Keiko
authors: K
authors: Wakui
authors: Yoshimitsu
authors: Y
authors: Fukushima
authors: Fumio
authors: F
authors: Kishi
authors: Kunihiro
authors: K
authors: Hamamoto
authors: Masaru
authors: M
authors: Terai
authors: Yoshitake
authors: Y
authors: Sato
authors: Kazunobu
authors: K
authors: Ouchi
authors: Tsutomu
authors: T
authors: Saji
authors: Akiyoshi
authors: A
authors: Nariai
authors: Yoichi
authors: Y
authors: Kaburagi
authors: Tetsushi
authors: T
authors: Yoshikawa
authors: Kyoko
authors: K
authors: Suzuki
authors: Takeo
authors: T
authors: Tanaka
authors: Toshiro
authors: T
authors: Nagai
authors: Hideo
authors: H
authors: Cho
authors: Akihiro
authors: A
authors: Fujino
authors: Akihiro
authors: A
authors: Sekine
authors: Reiichiro
authors: R
authors: Nakamichi
authors: Tatsuhiko
authors: T
authors: Tsunoda
authors: Tomisaku
authors: T
authors: Kawasaki
authors: Yusuke
authors: Y
authors: Nakamura
authors: Akira
authors: A
authors: Hata
mesh_terms: D044466:Asian People / Q000235:genetics; D002888:Chromosomes, Human, Pair 19; D003323:Coronary Aneurysm / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008213:Lymphocyte Activation; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics* / Q000276:immunology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012326:RNA Splicing; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase