Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease
Journal
Nature Genetics
Journal Volume
43
Journal Issue
12
Pages
1241-1246
Date Issued
2011
Author(s)
Khor C.C.
Davila S.
Breunis W.B.
Lee Y.-C.
Shimizu C.
Wright V.J.
Yeung R.S.M.
Tan D.E.K.
Sim K.S.
Wang J.J.
Wong T.Y.
Pang J.
Mitchell P.
Cimaz R.
Dahdah N.
Cheung Y.-F.
Huang G.-Y.
Yang W.
Park I.-S.
Lee J.-K.
Wu J.-Y.
Levin M.
Burns J.C.
Burgner D.
Kuijpers T.W.
Hibberd M.L.
Lau Y.-L.
Zhang J.
Ma X.-J.
Liu F.
Wu L.
Yoo J.-J.
Hong S.-J.
Kim K.-J.
Kim J.-J.
Park Y.-M.
Hong Y.M.
Sohn S.
Jang G.Y.
Ha K.-S.
Nam H.-K.
Byeon J.-H.
Yun S.W.
Han M.K.
Lee K.-Y.
Hwang J.-Y.
Rhim J.-W.
Song M.S.
Lee H.-D.
Kim D.S.
Lee J.-M.
Chang J.-S.
Tsai F.-J.
Liang C.-D.
Chen M.-R.
Chi H.
Chiu N.-C.
Huang F.-Y.
Kuo H.-C.
Huang K.-P.
Lee M.-L.
Hwang B.
Huang Y.-C.
Lee P.-C.
Odam M.
Christiansen F.T.
Witt C.
Goldwater P.
Curtis N.
Palasanthiran P.
Ziegler J.
Nissen M.
Nourse C.
Kuipers I.M.
Ottenkamp J.J.
Geissler J.
Biezeveld M.
Tacke C.
Filippini L.
Brogan P.
Klein N.
Shah V.
Dillon M.
Booy R.
Shingadia D.
Bose A.
Mukasa T.
Tulloh R.
Michie C.
Newburger J.W.
Baker A.L.
Rowley A.H.
Shulman S.T.
Mason W.
Takahashi M.
Melish M.E.
Tremoulet A.H.
Viswanathan A.
Rochtchina E.
Attia J.
Scott R.
Holliday E.
Harrap S.
Abstract
Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 × 10 -11, odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 × 10 -9, OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 × 10 -12, OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings. The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease. ? 2011 Nature America, Inc. All rights reserved.
SDGs
Other Subjects
arginine; Fc receptor IIa; histidine; allele; amino acid substitution; article; child; chromosome 19q; controlled study; disease predisposition; fcgr 2a gene; gene; gene locus; genetic association; genetic risk; genetic susceptibility; human; major clinical study; mucocutaneous lymph node syndrome; nucleotide sequence; priority journal; single nucleotide polymorphism; Case-Control Studies; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Haplotypes; Humans; Linkage Disequilibrium; Mucocutaneous Lymph Node Syndrome; Multigene Family; Polymorphism, Single Nucleotide; Principal Component Analysis; Receptors, IgG
Type
journal article