Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
Department of Pediatrics, Chung-Ang University Hospital, Seoul, Korea.
J Hum Genet. 2017 Dec;62(12):1023-1029. doi: 10.1038/jhg.2017.87. Epub 2017 Aug 31.
Kawasaki disease (KD), a systemic vasculitis of infants and children, manifests as fever and mucocutaneous inflammation. Although its etiology is largely unknown, the epidemiological data suggest that genetic factors are important in KD susceptibility. To identify genetic variants influencing KD susceptibility, we performed a genome-wide association study (GWAS) and replication study using a total of 915 children with KD and 4553 controls in the Korean population. Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (P<1.0 × 10), including the previously reported BLK locus (rs6993775, odds ratio (OR)=1.52, P=2.52 × 10). The other two loci were newly identified: NMNAT2 on chromosome 1q25.3 (rs2078087, OR=1.33, P=1.15 × 10) and the human leukocyte antigen (HLA) region on chromosome 6p21.3 (HLA-C, HLA-B, MICA and HCP5) (rs9380242, rs9378199, rs9266669 and rs6938467; OR=1.33-1.51, P=8.93 × 10 to 5.24 × 10). Additionally, SNP rs17280682 in NLRP14 was associated significantly with KD with a family history (18 cases vs 4553 controls, OR=6.76, P=5.46 × 10). These results provide new insights into the pathogenesis and pathophysiology of KD.
川崎病（KD）是一种婴儿和儿童全身性血管炎，表现为发热和黏膜皮肤炎症。尽管其病因在很大程度上尚不清楚，但流行病学数据表明，遗传因素在 KD 易感性中起重要作用。为了确定影响 KD 易感性的遗传变异，我们在韩国人群中进行了一项全基因组关联研究（GWAS）和复制研究，共纳入了 915 例 KD 患儿和 4553 名对照。三个基因座的 6 个单核苷酸多态性（SNPs）与 KD 易感性显著相关（P<1.0×10），包括先前报道的 BLK 基因座（rs6993775，优势比（OR）=1.52，P=2.52×10）。另外两个基因座是新发现的：染色体 1q25.3 上的 NMNAT2（rs2078087，OR=1.33，P=1.15×10）和染色体 6p21.3 上的人类白细胞抗原（HLA）区域（HLA-C、HLA-B、MICA 和 HCP5）（rs9380242、rs9378199、rs9266669 和 rs6938467；OR=1.33-1.51，P=8.93×10 至 5.24×10）。此外，NLRP14 中的 SNP rs17280682 与有家族史的 KD 显著相关（18 例 vs 4553 例对照，OR=6.76，P=5.46×10）。这些结果为 KD 的发病机制和病理生理学提供了新的见解。
