安川　久美    Department   School of Medicine(Yachiyo Medical Center), School of Medicine    Position   Associate Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Variations in ORAI1 Gene Associated with Kawasaki Disease.
Journal	Formal name：PloS one Abbreviation：PLoS One ISSN code：19326203/19326203
Domestic / Foregin	Foregin
Volume, Issue, Page	11(1),pp.e0145486
Author and coauthor	Onouchi Yoshihiro, Fukazawa Ryuji, Yamamura Kenichiro, Suzuki Hiroyuki, Kakimoto Nobuyuki, Suenaga Tomohiro, Takeuchi Takashi, Hamada Hiromichi, Honda Takafumi, Yasukawa Kumi, Terai Masaru, Ebata Ryota, Higashi Kouji, Saji Tsutomu, Kemmotsu Yasushi, Takatsuki Shinichi, Ouchi Kazunobu, Kishi Fumio, Yoshikawa Tetsushi, Nagai Toshiro, Hamamoto Kunihiro, Sato Yoshitake, Honda Akihito, Kobayashi Hironobu, Sato Junichi, Shibuta Shoichi, Miyawaki Masakazu, Oishi Ko, Yamaga Hironobu, Aoyagi Noriyuki, Yoshiyama Megumi, Miyashita Ritsuko, Murata Yuji, Fujino Akihiro, Ozaki Kouichi, Kawasaki Tomisaku, Abe Jun, Seki Mitsuru, Kobayashi Tohru, Arakawa Hirokazu, Ogawa Shunichi, Hara Toshiro, Hata Akira, Tanaka Toshihiro
Publication date	2016
Summary	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 Ca(2+)/NFAT pathway in the pathogenesis of KD. ORAI1 is a Ca(2+) release activated Ca(2+) (CRAC) channel mediating store-operated Ca(2+) 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 in-frame 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 Ca(2+)/NFAT pathway in the pathogenesis of this disorder.
DOI	10.1371/journal.pone.0145486
PMID	26789410