Journal
PLOS ONE
Volume 6, Issue 2, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0016853
Keywords
-
Categories
Funding
- National Science Council, Taiwan [NSC99-3112-B-001-022, NSC 98-2314-B-039-004-MY2]
- National Genotyping Center [NSC99-3112-B-001-023]
- Academia Sinica Genomic Medicine Multicenter Study, Taiwan [5202401129-3]
Ask authors/readers for more resources
Kawasaki disease (KD) is an acute systemic vasculitis syndrome that primarily affects infants and young children. Its etiology is unknown; however, epidemiological findings suggest that genetic predisposition underlies disease susceptibility. Taiwan has the third-highest incidence of KD in the world, after Japan and Korea. To investigate novel mechanisms that might predispose individuals to KD, we conducted a genome-wide association study (GWAS) in 250 KD patients and 446 controls in a Han Chinese population residing in Taiwan, and further validated our findings in an independent Han Chinese cohort of 208 cases and 366 controls. The most strongly associated single-nucleotide polymorphisms (SNPs) detected in the joint analysis corresponded to three novel loci. Among these KD-associated SNPs three were close to the COPB2 (coatomer protein complex beta-2 subunit) gene: rs1873668 (p=9.52x10(-5)), rs4243399 (p=9.93x10(-5)), and rs16849083 (p=9.93x10(-5)). We also identified a SNP in the intronic region of the ERAP1 (endoplasmic reticulum amino peptidase 1) gene (rs149481, p(best)=4.61x10(-5)). Six SNPs (rs17113284, rs8005468, rs10129255, rs2007467, rs10150241, and rs12590667) clustered in an area containing immunoglobulin heavy chain variable regions genes, with p(best)-values between 2.08x10(-5) and 8.93x10(-6), were also identified. This is the first KD GWAS performed in a Han Chinese population. The novel KD candidates we identified have been implicated in T cell receptor signaling, regulation of proinflammatory cytokines, as well as antibody-mediated immune responses. These findings may lead to a better understanding of the underlying molecular pathogenesis of KD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available