Common variants in CASP3 confer susceptibility to Kawasaki disease

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.; Yoshikawa, T.; Nagai, T.; Hamamoto, K.; Kishi, F.; Ouchi, K.; Sato, Y.; Newburger, J. W.; Baker, A. L.; Shulman, S. T.; Rowley, A. H.; Yashiro, M.; Nakamura, Y.; Wakui, K.; Fukushima, Y.; Fujino, A.; Tsunoda, T.; Kawasaki, T.; Hata, A.; Tanaka, T.

Hum Mol Genet. 2010 Apr 29; 19(14):2898-906

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 x 10(-8) in the Japanese and P = 3.7 x 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.

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