Open AccessIdentification of Novel Susceptibility Loci for Kawasaki Disease in a Han Chinese Population by a Genome-Wide Association Study
Author(s) -
Fuu Jen Tsai,
YiChing Lee,
JenPing Chang,
Li Min Huang,
Fu Yuan Huang,
Nan Chang Chiu,
Ming Ren Chen,
Hsin Chi,
Yann Jinn Lee,
Chang Li,
Yi Min Liu,
Hsiang Hua Wang,
Chien Hsiun Chen,
Yuan Tsong Chen,
Jer Yuarn Wu
Publication year - 2011
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0016853
Subject(s) - genome wide association study , single nucleotide polymorphism , genetics , snp , genetic association , genetic predisposition , biology , population , candidate gene , gene , medicine , immunology , genotype , environmental health
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 = 9.52×10 −5 ), rs4243399 ( p = 9.93×10 −5 ), and rs16849083 ( p = 9.93×10 −5 ). We also identified a SNP in the intronic region of the ERAP1 (endoplasmic reticulum amino peptidase 1) gene (rs149481, p best = 4.61×10 −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 2.08×10 −5 and 8.93×10 −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.