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

Authors
Khor, Chiea ChuenDavila, SoniaBreunis, Willemijn B.Lee, Yi-ChingShimizu, ChisatoWright, Victoria J.Yeung, Rae S. M.Tan, Dennis E. K.Sim, Kar SengWang, Jie JinWong, Tien YinPang, JunxiongMitchell, PaulCimaz, RolandoDahdah, NagibCheung, Yiu-FaiHuang, Guo-YingYang, WanlingPark, In-SookLee, Jong-KeukWu, Jer-YuarnLevin, MichaelBurns, Jane C.Burgner, DavidKuijpers, Taco W.Hibberd, Martin L.Lau, Yu-LungZhang, JingMa, Xiao-JingLiu, FangWu, LinYoo, Jeong-JinHong, Soo-JongKim, Kwi-JooKim, Jae-JungPark, Young-MiHong, Young MiSohn, SejungJang, Gi YoungHa, Kee-SooNam, Hyo-KyoungByeon, Jung-HyeYun, Sin WeonHan, Myung KiLee, Kyung-YilHwang, Ja-YoungRhim, Jung-WooSong, Min SeobLee, Hyoung-DooKim, Dong SooLee, Jae-MooChang, Jeng-ShengTsai, Fuu-JenLiang, Chi-DiChen, Ming-RenChi, HsinChiu, Nan-ChangHuang, Fu-YuanChang, Luan-YinHuang, Li-MinKuo, Ho-ChangHuang, Kao-PinLee, Meng-LuenHwang, BetauHuang, Yhu-CheringLee, Pi-ChangOdam, MirandaChristiansen, Frank T.Witt, CampbellGoldwater, PaulCurtis, NigelPalasanthiran, PamelaZiegler, JohnNissen, MichaelNourse, ClareKuipers, Irene M.Ottenkamp, Jaap J.Geissler, JudyBiezeveld, MaartenTacke, CarlineFilippini, LucBrogan, PaulKlein, NigelShah, VanitaDillon, MichaelBooy, RobertShingadia, DelaneBose, AnuMukasa, ThomasTulloh, RobertMichie, ColinNewburger, Jane W.Baker, Annette L.Rowley, Anne H.Shulman, Stanford T.Mason, WilbertTakahashi, MasatoMelish, Marian E.Tremoulet, Adriana H.Viswanathan, AnanthRochtchina, ElenaAttia, JohnScott, RodneyHolliday, ElizabethHarrap, Stephen
Issue Date
12월-2011
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE GENETICS, v.43, no.12, pp.1241 - 1246
Indexed
SCIE
SCOPUS
Journal Title
NATURE GENETICS
Volume
43
Number
12
Start Page
1241
End Page
1246
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/110977
DOI
10.1038/ng.981
ISSN
1061-4036
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 x 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 x 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 x 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.
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