Variations in ORAI1 gene associated with kawasaki disease

Yoshihiro Onouchi, Ryuji Fukazawa, Kenichiro Yamamura, Hiroyuki Suzuki, Nobuyuki Kakimoto, Tomohiro Suenaga, Takashi Takeuchi, Hiromichi Hamada, Takafumi Honda, Kumi Yasukawa, Masaru Terai, Ryota Ebata, Kouji Higashi, Tsutomu Saji, Yasushi Kemmotsu, Shinichi Takatsuki, Kazunobu Ouchi, Fumio Kishi, Tetsushi Yoshikawa, Toshiro NagaiKunihiro Hamamoto, Yoshitake Sato, Akihito Honda, Hironobu Kobayashi, Junichi Sato, Shoichi Shibuta, Masakazu Miyawaki, Ko Oishi, Hironobu Yamaga, Noriyuki Aoyagi, Megumi Yoshiyama, Ritsuko Miyashita, Yuji Murata, Akihiro Fujino, Kouichi Ozaki, Tomisaku Kawasaki, Jun Abe, Mitsuru Seki, Tohru Kobayashi, Hirokazu Arakawa, Shunichi Ogawa, Toshiro Hara, Akira Hata, Toshihiro Tanaka

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Kawasaki disease (KD; MIM#61175) is a systemic vasculitis syndrome with unknown etiology which predominantly affects infants and children. Recent findings of susceptibility genes for KD suggest possible involvement of the Ca2+/NFAT pathway in the pathogenesis of KD. ORAI1 is a Ca2+ release activated Ca2+ (CRAC) channel mediating store-operated Ca2+ entry (SOCE) on the plasma membrane. The gene for ORAI1 is located in chromosome 12q24 where a positive linkage signal was observed in our previous affected sib-pair study of KD. A common non-synonymous single nucleotide polymorphism located within exon 2 of ORAI1 (rs3741596) was significantly associated with KD (P = 0.028 in the discovery sample set (729 KD cases and 1,315 controls), P = 0.0056 in the replication sample set (1,813 KD cases vs. 1,097 controls) and P = 0.00041 in a meta-Analysis by the Mantel-Haenszel method). Interestingly, frequency of the risk allele of rs3741596 is more than 20 times higher in Japanese compared to Europeans. We also found a rare 6 base-pair inframe insertion variant associated with KD (rs141919534; 2,544 KD cases vs. 2,414 controls, P = 0.012). These data indicate that ORAI1 gene variations are associated with KD and may suggest the potential importance of the Ca2+/NFAT pathway in the pathogenesis of this disorder.

Original languageEnglish
Article numbere0145486
JournalPloS one
Volume11
Issue number1
DOIs
Publication statusPublished - 01-01-2016

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Variations in ORAI1 gene associated with kawasaki disease'. Together they form a unique fingerprint.

  • Cite this

    Onouchi, Y., Fukazawa, R., Yamamura, K., Suzuki, H., Kakimoto, N., Suenaga, T., Takeuchi, T., Hamada, H., Honda, T., Yasukawa, K., Terai, M., Ebata, R., Higashi, K., Saji, T., Kemmotsu, Y., Takatsuki, S., Ouchi, K., Kishi, F., Yoshikawa, T., ... Tanaka, T. (2016). Variations in ORAI1 gene associated with kawasaki disease. PloS one, 11(1), [e0145486]. https://doi.org/10.1371/journal.pone.0145486