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 Suzuki; Takeo Tanaka; Toshiro Nagai; Hideo Cho; Akihiro Fujino; Akihiro Sekine; Reiichiro Nakamichi; Tatsuhiko Tsunoda; Tomisaku Kawasaki; Yusuke Nakamura; Akira Hata

doi:10.1038/ng.2007.59

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 Suzuki

Takeo Tanaka, Toshiro Nagai, Hideo Cho, Akihiro Fujino, Akihiro Sekine, Reiichiro Nakamichi, Tatsuhiko Tsunoda, Tomisaku Kawasaki, Yusuke Nakamura, Akira Hata

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

442 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	英語
ページ（範囲）	35-42
ページ数	8
ジャーナル	Nature Genetics
巻	40
号	1
DOI	https://doi.org/10.1038/ng.2007.59
出版ステータス	出版済み - 01-2008
外部発表	はい

All Science Journal Classification (ASJC) codes

遺伝学

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10.1038/ng.2007.59

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Onouchi, Y., Gunji, T., Burns, J. C., Shimizu, C., Newburger, J. W., Yashiro, M., Nakamura, Y., Yanagawa, H., Wakui, K., Fukushima, Y., Kishi, F., Hamamoto, K., Terai, M., Sato, Y., Ouchi, K., Saji, T., Nariai, A., Kaburagi, Y., Yoshikawa, T., ... Hata, A. (2008). ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms. Nature Genetics, 40(1), 35-42. https://doi.org/10.1038/ng.2007.59

@article{c3d8e50aab5a4bf58b5f584e5991aeef,

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.",

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

note = "Funding Information: We thank the individuals with Kawasaki disease and their families who participated in this project. We are grateful to H. Aotsuka, H. Nakajima, F. Kudo, M. Miura, K. Akagi, T. Matsubara, M. Nishibatake, S. Oku, K. Sameshima, Y. Tanaka, Y. Nomura, S. Ogita, M. Sakauchi, T. Isobe, T. Sano, T. Matsushita and other physicians who contributed DNA samples. We thank J. Pancheri and A. Baker for collection of DNA samples and D. Scherrer, H. Sugiyama and M. Saito for technical assistance. This work was supported by grants from",

year = "2008",

month = jan,

doi = "10.1038/ng.2007.59",

language = "English",

volume = "40",

pages = "35--42",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "1",

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Onouchi, Y, Gunji, T, Burns, JC, Shimizu, C, Newburger, JW, Yashiro, M, Nakamura, Y, Yanagawa, H, Wakui, K, Fukushima, Y, Kishi, F, Hamamoto, K, Terai, M, Sato, Y, Ouchi, K, Saji, T, Nariai, A, Kaburagi, Y, Yoshikawa, T, Suzuki, K, Tanaka, T, Nagai, T, Cho, H, Fujino, A, Sekine, A, Nakamichi, R, Tsunoda, T, Kawasaki, T, Nakamura, Y & Hata, A 2008, 'ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms', Nature Genetics, vol. 40, no. 1, pp. 35-42. https://doi.org/10.1038/ng.2007.59

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T1 - ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms

AU - Onouchi, Yoshihiro

AU - Gunji, Tomohiko

AU - Burns, Jane C.

AU - Shimizu, Chisato

AU - Newburger, Jane W.

AU - Yashiro, Mayumi

AU - Nakamura, Yoshikazu

AU - Yanagawa, Hiroshi

AU - Wakui, Keiko

AU - Fukushima, Yoshimitsu

AU - Kishi, Fumio

AU - Hamamoto, Kunihiro

AU - Terai, Masaru

AU - Sato, Yoshitake

AU - Ouchi, Kazunobu

AU - Saji, Tsutomu

AU - Nariai, Akiyoshi

AU - Kaburagi, Yoichi

AU - Yoshikawa, Tetsushi

AU - Suzuki, Kyoko

AU - Tanaka, Takeo

AU - Nagai, Toshiro

AU - Cho, Hideo

AU - Fujino, Akihiro

AU - Sekine, Akihiro

AU - Nakamichi, Reiichiro

AU - Tsunoda, Tatsuhiko

AU - Kawasaki, Tomisaku

AU - Nakamura, Yusuke

AU - Hata, Akira

N1 - Funding Information: We thank the individuals with Kawasaki disease and their families who participated in this project. We are grateful to H. Aotsuka, H. Nakajima, F. Kudo, M. Miura, K. Akagi, T. Matsubara, M. Nishibatake, S. Oku, K. Sameshima, Y. Tanaka, Y. Nomura, S. Ogita, M. Sakauchi, T. Isobe, T. Sano, T. Matsushita and other physicians who contributed DNA samples. We thank J. Pancheri and A. Baker for collection of DNA samples and D. Scherrer, H. Sugiyama and M. Saito for technical assistance. This work was supported by grants from

PY - 2008/1

Y1 - 2008/1

N2 - 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.

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

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