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Variations in ORAI1 Gene Associated with Kawasaki Disease.

Authors :
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 Nagai
Kunihiro 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
Source :
PLoS ONE, Vol 11, Iss 1, p e0145486 (2016)
Publication Year :
2016
Publisher :
Public Library of Science (PLoS), 2016.

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 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.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
19326203
Volume :
11
Issue :
1
Database :
Directory of Open Access Journals
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
edsdoj.87e36abd0b434850ad3d951957d0c072
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pone.0145486