|Title:||Identification of novel susceptibility loci for Kawasaki disease in a han Chinese population by a genome-wide association study||Authors:||Tsai F.-J.
|Issue Date:||2011||Journal Volume:||6||Journal Issue:||2||Start page/Pages:||e16853||Source:||PLoS ONE||Abstract:||
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, pbest = 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 pbest-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. ? 2011 Tsai et al.
|ISSN:||1932-6203||DOI:||10.1371/journal.pone.0016853||SDG/Keyword:||cell protein; coatomer protein; coatomer protein complex beta 2 subunit; endoplasmic reticulum amino peptidase 1; glutamate carboxypeptidase II; HLA A antigen; HLA B antigen; immunoglobulin heavy chain; mitochondrial protein; mitochondrial ribosomal protein S22; retinol binding protein; retinol binding protein 2; tumor necrosis factor alpha; unclassified drug; article; Chinese; controlled study; gene frequency; gene linkage disequilibrium; gene locus; genetic association; genetic predisposition; genetic susceptibility; genotype; haplotype map; human; immune response; intron; major clinical study; mucocutaneous lymph node syndrome; phenotype; risk factor; single nucleotide polymorphism; Taiwan; Asian; case control study; ethnology; female; genetic association; genetic predisposition; genetics; infant; male; population genetics; preschool child; validation study; Asian Continental Ancestry Group; Case-Control Studies; Child, Preschool; Female; Genetic Loci; Genetic Predisposition to Disease; Genetics, Population; Genome-Wide Association Study; Genotype; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Polymorphism, Single Nucleotide
|Appears in Collections:||醫學系|
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