Common variants in CASP3 confer susceptibility to Kawasaki disease.
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.
Onouchi
Yoshihiro
Y
Laboratory for Cardiovascular diseases, Center for Genomic Medicine RIKEN, Yokohama 230-0045, Japan. onouchi@src.riken.jp
Ozaki
Kouichi
K
Buns
Jane C
JC
Shimizu
Chisato
C
Hamada
Hiromichi
H
Honda
Takafumi
T
Terai
Masaru
M
Honda
Akihito
A
Takeuchi
Takashi
T
Shibuta
Shoichi
S
Suenaga
Tomohiro
T
Suzuki
Hiroyuki
H
Higashi
Kouji
K
Yasukawa
Kumi
K
Suzuki
Yoichi
Y
Sasago
Kumiko
K
Kemmotsu
Yasushi
Y
Takatsuki
Shinichi
S
Saji
Tsutomu
T
Yoshikawa
Tetsushi
T
Nagai
Toshiro
T
Hamamoto
Kunihiro
K
Kishi
Fumio
F
Ouchi
Kazunobu
K
Sato
Yoshitake
Y
Newburger
Jane W
JW
Baker
Annette L
AL
Shulman
Stanford T
ST
Rowley
Anne H
AH
Yashiro
Mayumi
M
Nakamura
Yoshikazu
Y
Wakui
Keiko
K
Fukushima
Yoshimitsu
Y
Fujino
Akihiro
A
Tsunoda
Tatsuhiko
T
Kawasaki
Tomisaku
T
Hata
Akira
A
Nakamura
Yusuke
Y
Tanaka
Toshihiro
T
D000328:Adult; D044466:Asian People / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics*; D050778:NFATC Transcription Factors / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011485:Protein Binding; D044465:White People / Q000235:genetics
D050778:NFATC Transcription Factors; C505407:CASP3 protein, human; D053148:Caspase 3