title: Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease.
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(1). 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.
authors.affiliation: Infectious Diseases, Genome Institute of Singapore, Singapore.
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.forename: Sonia
authors.initials: S
authors.lastname: Davila
authors.forename: Willemijn B
authors.initials: WB
authors.lastname: Breunis
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Lee
authors.forename: Chisato
authors.initials: C
authors.lastname: Shimizu
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Wright
authors.forename: Rae S M
authors.initials: RS
authors.lastname: Yeung
authors.forename: Dennis E K
authors.initials: DE
authors.lastname: Tan
authors.forename: Kar Seng
authors.initials: KS
authors.lastname: Sim
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.forename: Tien Yin
authors.initials: TY
authors.lastname: Wong
authors.forename: Junxiong
authors.initials: J
authors.lastname: Pang
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.forename: Rolando
authors.initials: R
authors.lastname: Cimaz
authors.forename: Nagib
authors.initials: N
authors.lastname: Dahdah
authors.forename: Yiu-Fai
authors.initials: YF
authors.lastname: Cheung
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Huang
authors.forename: Wanling
authors.initials: W
authors.lastname: Yang
authors.forename: In-Sook
authors.initials: IS
authors.lastname: Park
authors.forename: Jong-Keuk
authors.initials: JK
authors.lastname: Lee
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
authors.forename: Jane C
authors.initials: JC
authors.lastname: Burns
authors.forename: David
authors.initials: D
authors.lastname: Burgner
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
mesh_terms: D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics*; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D017452:Receptors, IgG / Q000235:genetics*
chemical_list: C445323:FCGR2A protein, human; D017452:Receptors, IgG
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