Common variants in CASP3 confer susceptibility to Kawasaki disease

• Published in: Human molecular genetics Vol. 19; no. 14; pp. 2898 - 2906
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.07.2010
• Subjects: Adult; Asian Continental Ancestry Group - genetics; Association Studies; Binding Sites - genetics; Biological and medical sciences; Case-Control Studies; Caspase 3 - genetics; Caspase 3 - metabolism; Caspase 3 - physiology; Child; Child, Preschool; European Continental Ancestry Group - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genetic Predisposition to Disease; Genetic Testing; Genetics of eukaryotes. Biological and molecular evolution; Humans; Infant; Linkage Disequilibrium; Male; Medical sciences; Molecular and cellular biology; Mucocutaneous Lymph Node Syndrome - genetics; NFATC Transcription Factors - metabolism; Polymorphism, Single Nucleotide - physiology; Protein Binding; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Vascular disease; Kawasaki syndrome; Variant; Immunopathology; Vasculitis; Systemic disease; Autoimmune disease; Cardiovascular disease; Genetics
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/ddq176

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 suggest that altered CASP3 expression in immune effecter cells influences susceptibility to KD.