A genome-wide association analysis reveals 1p31 and 2p13.3 as susceptibility loci for Kawasaki disease
A genome-wide association analysis reveals 1p31 and 2p13.3 as susceptibility loci for Kawasaki disease
复制标题
DOI：
10.1007/s00439-010-0937-x
复制
发表时间：
2011-05-01
期刊：
影响因子：
5.3
通讯作者：
Lee, Jong-Keuk
中科院分区：
文献类型：
--
作者：
Kim, Jae-Jung;Hong, Young Mi;Lee, Jong-Keuk
川崎（KD）是一种急性自限性血管炎的婴儿和儿童，表现为发烧和粘膜皮肤炎症的迹象。在未经治疗的儿童中，约有15-25%发生冠状动脉瘤。虽然KD的病因在很大程度上是未知的，流行病学数据表明遗传因素在KD易感性中的重要性。为了确定影响KD易感性的遗传变异，我们使用Affyssin SNP阵列6.0对186名韩国KD患者和600名健康对照进行了全基因组关联研究（GWAS）; 18个和26个基因组区域中的一个或多个序列变异分别与KD和KD伴冠状动脉病变（CAL）相关（p < 1 × 10 - 5）。其中，染色体1 p31上的一个位点rs 527409基因在266例KD患儿和600例正常对照组中重复检测（比值比[OR] = 2.90，95%置信区间[CI] = 1.85-4.54，P（合并）= 1.46 × 10（-6））;在86例伴CAL的KD患者和600例对照组中，PELI 1基因在染色体2p13.3（rs7604693）上重复（OR = 2.70，95% CI = 1.77-4.12，Pcombined = 2.00 × 10 - 6）。这些结果暗示1 p31区域中的一个位点和2p13.3区域中的PELI 1基因位点分别为KD和CAL的易感位点。
Kawasaki disease (KD) is an acute self-limited vasculitis of infants and children that manifests as fever and signs of mucocutaneous inflammation. Coronary artery aneurysms develop in approximately 15-25% of untreated children. Although the etiology of KD is largely unknown, epidemiologic data suggest the importance of genetic factors in the susceptibility to KD. In order to identify genetic variants that influence KD susceptibility, we performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 186 Korean KD patients and 600 healthy controls; 18 and 26 genomic regions with one or more sequence variants were associated with KD and KD with coronary artery lesions (CALs), respectively (p < 1 x 10(-5)). Of these, one locus on chromosome 1p31 (rs527409) was replicated in 266 children with KD and 600 normal controls (odds ratio [OR] = 2.90, 95% confidence interval [CI] = 1.85-4.54, P(combined) = 1.46 x 10(-6)); and a PELI1 locus on chromosome 2p13.3 (rs7604693) was replicated in 86 KD patients with CALs and 600 controls (OR = 2.70, 95% CI = 1.77-4.12, Pcombined = 2.00 x 10(-6)). These results implicate a locus in the 1p31 region and the PELI1 gene locus in the 2p13.3 region as susceptibility loci for KD and CALs, respectively.