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 YoshikawaToshiro 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

94 Citations (Scopus)

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 - 2010 Apr 27

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Common variants in CASP3 confer susceptibility to Kawasaki disease'. Together they form a unique fingerprint.

  • Cite this

    Onouchi, Y., Ozaki, K., Buns, J. C., 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., ... 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