Common variants in CASP3 confer susceptibility to Kawasaki disease

Yoshihiro Onouchi, Kouichi Ozaki, Jane C. Buns, Chisato Shimizu, Hiromichi Hamada, Takafumi Honda, Masaru Terai, Akihito Honda, Takashi Takeuchi, Shoichi Shibuta, Tomohiro Suenaga, Hiroyuki Suzuki, Kouji Higashi, Kumi Yasukawa, Yoichi Suzuki, Kumiko Sasago, Yasushi Kemmotsu, Shinichi Takatsuki, Tsutomu Saji, Tetsushi Yoshikawa & 19 others Toshiro Nagai, Kunihiro Hamamoto, Fumio Kishi, Kazunobu Ouchi, Yoshitake Sato, Jane W. Newburger, Annette L. Baker, Stanford T. Shulman, Anne H. Rowley, Mayumi Yashiro, Yoshikazu Nakamura, Keiko Wakui, Yoshimitsu Fukushima, Akihiro Fujino, Tatsuhiko Tsunoda, Tomisaku Kawasaki, Akira Hata, Yusuke Nakamura, Toshihiro Tanaka

Research output: Contribution to journalArticle

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Abstract

Kawasaki disease (KD; OMIM 611775) is an acute vasculitis syndrome which predominantly affects small-and medium-sized arteries of infants and children. Epidemiological data suggest that host genetics underlie the disease pathogenesis. Here we report that multiple variants in the caspase-3 gene (CASP3) that are in linkage disequilibrium confer susceptibility to KD in both Japanese and US subjects of European ancestry. We found that a G to A substitution of one commonly associated SNP located in the 5′ untranslated region of CASP3 (rs72689236; P = 4.2 × 10-8 in the Japanese and P = 3.7 × 10-3 in the European Americans) abolished binding of nuclear factor of activated T cells to the DNA sequence surrounding the SNP. Our findings suggestthat altered CASP3 expression in immune effecter cells influences susceptibility to KD.

Original languageEnglish
Article numberddq176
Pages (from-to)2898-2906
Number of pages9
JournalHuman molecular genetics
Volume19
Issue number14
DOIs
Publication statusPublished - 27-04-2010

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Mucocutaneous Lymph Node Syndrome
Caspase 3
Single Nucleotide Polymorphism
Genes
NFATC Transcription Factors
Genetic Databases
Inborn Genetic Diseases
5' Untranslated Regions
Linkage Disequilibrium
Vasculitis
Arteries
Gene Expression

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Onouchi, Y., Ozaki, K., Buns, J. C., Shimizu, C., Hamada, H., Honda, T., ... Tanaka, T. (2010). Common variants in CASP3 confer susceptibility to Kawasaki disease. Human molecular genetics, 19(14), 2898-2906. [ddq176]. https://doi.org/10.1093/hmg/ddq176
Onouchi, Yoshihiro ; Ozaki, Kouichi ; Buns, Jane C. ; Shimizu, Chisato ; Hamada, Hiromichi ; Honda, Takafumi ; Terai, Masaru ; Honda, Akihito ; Takeuchi, Takashi ; Shibuta, Shoichi ; Suenaga, Tomohiro ; Suzuki, Hiroyuki ; Higashi, Kouji ; Yasukawa, Kumi ; Suzuki, Yoichi ; Sasago, Kumiko ; Kemmotsu, Yasushi ; Takatsuki, Shinichi ; Saji, Tsutomu ; Yoshikawa, Tetsushi ; Nagai, Toshiro ; Hamamoto, Kunihiro ; Kishi, Fumio ; Ouchi, Kazunobu ; Sato, Yoshitake ; Newburger, Jane W. ; Baker, Annette L. ; Shulman, Stanford T. ; Rowley, Anne H. ; Yashiro, Mayumi ; Nakamura, Yoshikazu ; Wakui, Keiko ; Fukushima, Yoshimitsu ; Fujino, Akihiro ; Tsunoda, Tatsuhiko ; Kawasaki, Tomisaku ; Hata, Akira ; Nakamura, Yusuke ; Tanaka, Toshihiro. / Common variants in CASP3 confer susceptibility to Kawasaki disease. In: Human molecular genetics. 2010 ; Vol. 19, No. 14. pp. 2898-2906.
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Onouchi, Y, Ozaki, K, Buns, JC, Shimizu, C, Hamada, H, Honda, T, Terai, M, Honda, A, Takeuchi, T, Shibuta, S, Suenaga, T, Suzuki, H, Higashi, K, Yasukawa, K, Suzuki, Y, Sasago, K, Kemmotsu, Y, Takatsuki, S, Saji, T, Yoshikawa, T, Nagai, T, Hamamoto, K, Kishi, F, Ouchi, K, Sato, Y, Newburger, JW, Baker, AL, Shulman, ST, Rowley, AH, Yashiro, M, Nakamura, Y, Wakui, K, Fukushima, Y, Fujino, A, Tsunoda, T, Kawasaki, T, Hata, A, Nakamura, Y & Tanaka, T 2010, 'Common variants in CASP3 confer susceptibility to Kawasaki disease', Human molecular genetics, vol. 19, no. 14, ddq176, pp. 2898-2906. https://doi.org/10.1093/hmg/ddq176

Common variants in CASP3 confer susceptibility to Kawasaki disease. / Onouchi, Yoshihiro; Ozaki, Kouichi; Buns, Jane C.; Shimizu, Chisato; Hamada, Hiromichi; Honda, Takafumi; Terai, Masaru; Honda, Akihito; Takeuchi, Takashi; Shibuta, Shoichi; Suenaga, Tomohiro; Suzuki, Hiroyuki; Higashi, Kouji; Yasukawa, Kumi; Suzuki, Yoichi; Sasago, Kumiko; Kemmotsu, Yasushi; Takatsuki, Shinichi; Saji, Tsutomu; Yoshikawa, Tetsushi; Nagai, Toshiro; Hamamoto, Kunihiro; Kishi, Fumio; Ouchi, Kazunobu; Sato, Yoshitake; Newburger, Jane W.; Baker, Annette L.; Shulman, Stanford T.; Rowley, Anne H.; Yashiro, Mayumi; Nakamura, Yoshikazu; Wakui, Keiko; Fukushima, Yoshimitsu; Fujino, Akihiro; Tsunoda, Tatsuhiko; Kawasaki, Tomisaku; Hata, Akira; Nakamura, Yusuke; Tanaka, Toshihiro.

In: Human molecular genetics, Vol. 19, No. 14, ddq176, 27.04.2010, p. 2898-2906.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Common variants in CASP3 confer susceptibility to Kawasaki disease

AU - Onouchi, Yoshihiro

AU - Ozaki, Kouichi

AU - Buns, Jane C.

AU - Shimizu, Chisato

AU - Hamada, Hiromichi

AU - Honda, Takafumi

AU - Terai, Masaru

AU - Honda, Akihito

AU - Takeuchi, Takashi

AU - Shibuta, Shoichi

AU - Suenaga, Tomohiro

AU - Suzuki, Hiroyuki

AU - Higashi, Kouji

AU - Yasukawa, Kumi

AU - Suzuki, Yoichi

AU - Sasago, Kumiko

AU - Kemmotsu, Yasushi

AU - Takatsuki, Shinichi

AU - Saji, Tsutomu

AU - Yoshikawa, Tetsushi

AU - Nagai, Toshiro

AU - Hamamoto, Kunihiro

AU - Kishi, Fumio

AU - Ouchi, Kazunobu

AU - Sato, Yoshitake

AU - Newburger, Jane W.

AU - Baker, Annette L.

AU - Shulman, Stanford T.

AU - Rowley, Anne H.

AU - Yashiro, Mayumi

AU - Nakamura, Yoshikazu

AU - Wakui, Keiko

AU - Fukushima, Yoshimitsu

AU - Fujino, Akihiro

AU - Tsunoda, Tatsuhiko

AU - Kawasaki, Tomisaku

AU - Hata, Akira

AU - Nakamura, Yusuke

AU - Tanaka, Toshihiro

PY - 2010/4/27

Y1 - 2010/4/27

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AB - Kawasaki disease (KD; OMIM 611775) is an acute vasculitis syndrome which predominantly affects small-and medium-sized arteries of infants and children. Epidemiological data suggest that host genetics underlie the disease pathogenesis. Here we report that multiple variants in the caspase-3 gene (CASP3) that are in linkage disequilibrium confer susceptibility to KD in both Japanese and US subjects of European ancestry. We found that a G to A substitution of one commonly associated SNP located in the 5′ untranslated region of CASP3 (rs72689236; P = 4.2 × 10-8 in the Japanese and P = 3.7 × 10-3 in the European Americans) abolished binding of nuclear factor of activated T cells to the DNA sequence surrounding the SNP. Our findings suggestthat altered CASP3 expression in immune effecter cells influences susceptibility to KD.

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Onouchi Y, Ozaki K, Buns JC, Shimizu C, Hamada H, Honda T et al. Common variants in CASP3 confer susceptibility to Kawasaki disease. Human molecular genetics. 2010 Apr 27;19(14):2898-2906. ddq176. https://doi.org/10.1093/hmg/ddq176