Genetic variants in the HLA-G region are associated with Kawasaki disease.
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.
Kim
Jae-Jung
JJ
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
Hong
Soo-Jong
SJ
Hong
Young Mi
YM
Kim
Sun
S
Kang
Mi-Jin
MJ
Kim
Kwi-Joo
KJ
Seo
Eul-Joo
EJ
Yoo
Han-Wook
HW
Cheong
Hyun-Sub
HS
Shin
Hyoung-Doo
HD
Park
In-Sook
IS
Lee
Jong-Keuk
JK
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
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I