title: Genetic variants in the HLA-G region are associated with Kawasaki disease.
abstract: Kawasaki disease is an acute, self-limited vasculitis of infants and children, manifest as fever and signs of mucocutaneous inflammation. Treatment with high-dose immunoglobulin reduces systemic inflammation and prevents coronary artery lesions in Kawasaki disease. In this study, we investigated the possible association of the major histocompatibililty complex (MHC) region for the susceptibility to Kawasaki disease using an MHC panel of 2360 single nucleotide polymorphism (SNP) markers. Analysis of data obtained from screening MHC-specific SNP chips with 48 case and 90 control subjects revealed five candidate loci with significance levels of uncorrected p < 0.01. However, only one candidate locus (HLA-G) was confirmed to have a significant association with Kawasaki disease (rs2523790, odds ratio [OR] = 3.00, 95% confidence interval [95% CI] = 1.14-7.91, uncorrected p = 0.0263) in the replication study using 44 new case subjects and the previous 90 controls. In the fine mapping of the HLA-G locus, in particular, a nonsynonymous SNP (C/A) of the HLA-G gene (rs12722477, Leu134Ile) was significantly associated with Kawasaki disease (OR = 3.23, 95% CI = 1.12-9.32). A subgroup analysis showed that this association was more apparent in patients with coronary artery aneurysms (OR = 4.02, 95% CI = 1.23-13.19). Therefore, our results indicate that HLA-G may play a crucial role for the susceptibility to Kawasaki disease.
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jae-Jung
authors.initials: JJ
authors.lastname: Kim
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Hong
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Hong
authors.forename: Sun
authors.initials: S
authors.lastname: Kim
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Kang
authors.forename: Kwi-Joo
authors.initials: KJ
authors.lastname: Kim
authors.forename: Eul-Joo
authors.initials: EJ
authors.lastname: Seo
authors.forename: Han-Wook
authors.initials: HW
authors.lastname: Yoo
authors.forename: Hyun-Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Hyoung-Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: In-Sook
authors.initials: IS
authors.lastname: Park
authors.forename: Jong-Keuk
authors.initials: JK
authors.lastname: Lee
mesh_terms: D002874:Chromosome Mapping; D003323:Coronary Aneurysm / Q000209:etiology / Q000235:genetics; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005858:Germany; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D015810:Linkage Disequilibrium; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide
chemical_list: D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I