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

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

in Agriculture / Aneurysms / Animal Genetics and Genomics / Asian People - genetics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cardiology. Vascular system / Cardiovascular disease / Chromosomes / Chromosomes, Human, Pair 19 / Coronary Aneurysm - genetics / Coronary heart disease / Diagnosis / Etiology / Fundamental and applied biological sciences. Psychology / Gene Function / Genetic aspects / Genetic Predisposition to Disease / Genetics / Genetics of eukaryotes. Biological and molecular evolution / Heart / Human Genetics / Humans / Identification and classification / Kawasaki disease / Lesions / Linkage Disequilibrium / Lymphocyte Activation / Medical sciences / Mucocutaneous Lymph Node Syndrome - genetics / Mucocutaneous Lymph Node Syndrome - immunology / Pediatrics / Phosphotransferases (Alcohol Group Acceptor) - genetics / Physiological aspects / Polymorphism, Genetic / Polymorphism, Single Nucleotide / Ribonucleic acid / Risk factors / RNA / RNA Splicing / Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis / Signal transduction / Single nucleotide polymorphisms / T-Lymphocytes - immunology

2008

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

2008

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2008

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Journal Article

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

Yoshikawa, Tetsushi,

Fukushima, Yoshimitsu,

Kawasaki, Tomisaku,

Nakamichi, Reiichiro,

Tanaka, Takeo,

Nariai, Akiyoshi,

Sato, Yoshitake,

Nakamura, Yusuke,

Hamamoto, Kunihiro,

Fujino, Akihiro,

Newburger, Jane W,

Tsunoda, Tatsuhiko,

Yanagawa, Hiroshi,

Terai, Masaru,

Yashiro, Mayumi,

Suzuki, Kyoko,

Burns, Jane C,

Gunji, Tomohiko,

Onouchi, Yoshihiro,

Kishi, Fumio,

Saji, Tsutomu,

Sekine, Akihiro,

Kaburagi, Yoichi,

Cho, Hideo,

Wakui, Keiko,

Nakamura, Yoshikazu,

Shimizu, Chisato,

Hata, Akira,

Ouchi, Kazunobu,

Nagai, Toshiro

2008

Overview

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 Ca 2+ /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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Publisher

Nature Publishing Group US,Nature Publishing Group

Subject

Agriculture

/ Aneurysms

/ Animal Genetics and Genomics

/ Asian People - genetics

/ Biological and medical sciences

/ Biomedical and Life Sciences

/ Biomedicine