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Variations in ORAI1 Gene Associated with Kawasaki Disease.
- Source :
-
PloS one [PLoS One] 2016 Jan 20; Vol. 11 (1), pp. e0145486. Date of Electronic Publication: 2016 Jan 20 (Print Publication: 2016). - Publication Year :
- 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 :
- Adolescent
Calcium metabolism
Chromosomes, Human, Pair 12 genetics
Female
Gene Frequency
Genetic Predisposition to Disease genetics
Humans
Japan
Male
Mucocutaneous Lymph Node Syndrome pathology
ORAI1 Protein
Siblings
White People genetics
Young Adult
Asian People genetics
Calcium Channels genetics
Mucocutaneous Lymph Node Syndrome genetics
Mutagenesis, Insertional
Polymorphism, Single Nucleotide
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 26789410
- Full Text :
- https://doi.org/10.1371/journal.pone.0145486