Kim Jae-Jung, Hong Soo-Jong, Hong Young Mi, Kim Sun, Kang Mi-Jin, Kim Kwi-Joo, Seo Eul-Joo, Yoo Han-Wook, Cheong Hyun-Sub, Shin Hyoung-Doo, Park In-Sook, Lee Jong-Keuk
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
Hum Immunol. 2008 Dec;69(12):867-71. doi: 10.1016/j.humimm.2008.10.002. Epub 2008 Oct 29.
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.
川崎病是一种婴幼儿急性自限性血管炎，表现为发热和黏膜皮肤炎症体征。大剂量免疫球蛋白治疗可减轻川崎病的全身炎症并预防冠状动脉病变。在本研究中，我们使用包含2360个单核苷酸多态性（SNP）标记的主要组织相容性复合体（MHC）面板，调查了MHC区域与川崎病易感性之间的可能关联。对48例病例和90例对照受试者进行MHC特异性SNP芯片筛查所获得的数据进行分析，发现了5个显著性水平为未校正p<0.01的候选基因座。然而，在使用44例新病例受试者和之前的90例对照进行的重复研究中，只有一个候选基因座（HLA-G）被证实与川崎病有显著关联（rs2523790，比值比[OR]=3.00，95%置信区间[95%CI]=1.14-7.91，未校正p=0.0263）。特别是在HLA-G基因座的精细定位中，HLA-G基因的一个非同义SNP（C/A）（rs12722477，Leu134Ile）与川崎病显著相关（OR=3.23，95%CI=1.12-9.32）。亚组分析表明这种关联在冠状动脉瘤患者中更为明显（OR=4.02，95%CI=1.23-13.19）。因此，我们的结果表明HLA-G可能在川崎病易感性中起关键作用。
