Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Khor, CC; Davila, S; Breunis, WB; Lee, Y-C; Shimizu, C; Wright, VJ; Yeung, RSM; Tan, DEK; Sim, KS; Wang, JJ; Wong, TY; 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, JC; Burgner, D; Kuijpers, TW; Hibberd, ML; Hong Kong–Shanghai Kawasaki Disease Genetics Consortium, ; Korean Kawasaki Disease Genetics Consortium, ; Taiwan Kawasaki Disease Genetics Consortium, ; International Kawasaki Disease Genetics Consortium, ; US Kawasaki Disease Genetics Consortium, ; Blue Mountains Eye Study,

Published Date

  • December 2011

Published In

Volume / Issue

  • 43 / 12

Start / End Page

  • 1241 - 1246

PubMed ID

  • 22081228

Pubmed Central ID

  • 22081228

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng.981

Language

  • eng