Peng Qian, Chen Chang-hui, Wu Qing, Yang Yuan
Department of Pediatrics, Sichuan Provincial People's Hospital, Chengdu 610072, China.
Zhonghua Er Ke Za Zhi. 2013 Aug;51(8):571-7.
Kawasaki disease (KD) is a common autoimmune vasculitis. It has been regarded as the leading cause of acquired heart disease in children. This study aimed to assess the relationship between genome-wide association study (GWAS)-linked gene loci and KD.
By March of 2013, the published GWAS literatures of KD were retrieved from the databases including PubMed, MEDLINE, Web of Science, Cochrane Library, CNKI, VIP and Wanfang, and the gene loci associated with KD at genome-wide significance of P < 5.0×10(-8) were determined. For each of the gene loci, one single-nucleotide polymorphism (SNP) with strong association with KD was chosen for meta-analysis. Then the published case-control studies reporting the associations of the SNPs with KD were collected from English and Chinese databases with the same criteria. The Meta-analyses were conducted with RevMan 5.1 software after screening and evaluation.
A total of 4 gene loci including FCGR2A, BLK, CD40 and HLA were observed having association with KD at genome-wide significance of P < 5.0×10(-8) in at least one GWAS. The risk alleles of the SNPs in the gene loci were all more common in patients with KD relative to controls in the systematic reviews with 8, 4, 6 and 4 extracted case-control studies, respectively[ FCGR2A rs1801274: P < 0.001, OR = 1.40, 95% CI (1.30, 1.51); BLK rs2254546: P < 0.001, OR = 1.69, 95% CI (1.52, 1.88); CD40 rs4813003: P < 0.001, OR = 1.31, 95% CI (1.22, 1.41); HLA rs2857151: P < 0.001, OR = 1.41, 95% CI (1.27, 1.57)]. The significant publication bias was not observed in the meta-analyses.
Our results confirmed the overall association of the 4 gene loci with KD in observed populations, together with the consistent presence of the relationship between BLK or HLA and KD in the populations, suggesting that it is hopeful to find the genetic marker combination predicting the risk of KD, the formation of secondary coronary artery lesions and the resistance of intravenous immunoglobulin, by further seeking the function SNPs of the gene loci and investigating the effect on the important clinical phenotypes of KD.
川崎病（KD）是一种常见的自身免疫性血管炎。它被认为是儿童后天性心脏病的主要病因。本研究旨在评估全基因组关联研究（GWAS）相关基因位点与KD之间的关系。
截至2013年3月，从PubMed、MEDLINE、Web of Science、Cochrane图书馆、中国知网、维普和万方等数据库中检索已发表的KD的GWAS文献，并确定全基因组显著性水平为P<5.0×10⁻⁸的与KD相关的基因位点。对于每个基因位点，选择一个与KD关联较强的单核苷酸多态性（SNP）进行荟萃分析。然后按照相同标准从英文和中文数据库中收集报告这些SNP与KD关联的已发表病例对照研究。经筛选和评估后，使用RevMan 5.1软件进行荟萃分析。
在至少一项GWAS中，共观察到4个基因位点（FCGR2A、BLK、CD40和HLA）与KD存在全基因组显著性关联（P<5.0×10⁻⁸）。在分别提取了8、4、6和4项病例对照研究的系统评价中，这些基因位点中SNP的风险等位基因在KD患者中均比对照组更常见[FCGR2A rs1801274：P<0.001，OR = 1.40，95%CI（1.30，1.51）；BLK rs2254546：P<0.001，OR = 1.69，95%CI（1.52，1.88）；CD40 rs4813003：P<0.001，OR = 1.31，95%CI（1.22，1.41）；HLA rs2857151：P<0.001，OR = 1.41，95%CI（1.27，1.57）]。荟萃分析未观察到显著的发表偏倚。
我们的结果证实了这4个基因位点在观察人群中与KD的总体关联，以及在人群中BLK或HLA与KD之间关系的持续存在，这表明通过进一步寻找这些基因位点的功能性SNP并研究其对KD重要临床表型的影响，有望找到预测KD风险、继发性冠状动脉病变形成及静脉注射免疫球蛋白抵抗性的遗传标记组合。
