西亚试剂：Common variants in CASP3 confer susceptibility to Kawasaki

发布时间：2025-09-17

Common variants in CASP3 confer susceptibility to Kawasaki disease
Yoshihiro Onouchi1,*, Kouichi Ozaki1, Jane C. Buns2,3,25, Chisato Shimizu2,3,25, Hiromichi Hamada4, Takafumi Honda4, Masaru Terai4, Akihito Honda5, Takashi Takeuchi6, Shoichi Shibuta6, Tomohiro Suenaga6, Hiroyuki Suzuki6, Kouji Higashi7, Kumi Yasukawa7, Yoichi Suzuki8, Kumiko Sasago8, Yasushi Kemmotsu9, Shinichi Takatsuki9, Tsutomu Saji9, Tetsushi Yoshikawa10, Toshiro Nagai11, Kunihiro Hamamoto12, Fumio Kishi13, Kazunobu Ouchi14, Yoshitake Sato15, Jane W. Newburger16,25, Annette L. Baker16,25, Stanford T. Shulman17,25, Anne H. Rowley17,25, Mayumi Yashiro18, Yoshikazu Nakamura18, Keiko Wakui19, Yoshimitsu Fukushima19, Akihiro Fujino20, Tatsuhiko Tsunoda21, Tomisaku Kawasaki22, Akira Hata8, Yusuke Nakamura23,24 and Toshihiro Tanaka1

1 Laboratory for Cardiovascular diseases, Center for Genomic Medicine RIKEN, Yokohama 230-0045, Japan, 2 Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA, 3 Rady Children's Hospital San Diego, CA 92093-0641, USA, 4 Department of Pediatrics, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo 276-8524, Japan, 5 Department of Pediatrics, Asahi General Hospital, Asahi 289-2511, Japan, 6 Department of Pediatrics, Wakayama Medical University, Wakayama 641-0012, Japan, 7 Department of Pediatrics and 8 Department of Public Health, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan, 9 Department of Pediatrics, Toho University School of Medicine, Tokyo 143-8541, Japan, 10 Department of Pediatrics, Fujita Health University, Toyoake 470-1192, Japan, 11 Department of Pediatrics, Dokkyo Medical University, Koshigaya Hospital, Koshigaya 343-8555, Japan, 12 Department of Speech and Hearing Sciences, International University of health and welfare, Fukuoka 831-8501, Japan, 13 Department of Molecular Genetics and 14 Department of Pediatrics, Kawasaki Medical School, Kurashiki 701-0192, Japan, 15 Department of Pediatrics, Fuji Heavy Industry LTD, Health Insurance Society General Ohta Hospital, Ohta 373-8585, Japan, 16 Department of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA, 17 Department of Pediatrics, Feinberg School of Medicine Northwestern University, Children's Memorial Hospital, Chicago, IL 60611, USA, 18 Department of Public Health, Jichi Medical School, Minamikawachi 329-0498, Japan, 19 Department of Preventive Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan, 20 Department of Surgery, National Center for Child Health and Development, Tokyo 157-8535, Japan, 21 Laboratory for Medical Informatics, Center for Genomic Medicine, RIKEN, Yokohama 230-0045, Japan, 22 Japan Kawasaki Disease Research Center, Tokyo 101-0041, Japan, 23 Laboratory for Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan, 24 Center for Genomic Medicine RIKEN, Yokohama 230-0045, Japan and 25 U. S. KD Genetics Consortium

Kawasaki disease (KD; OMIM 611775 [OMIM] ) 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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