Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Hum Genet. 2013 Jun;132(6):669-80. doi: 10.1007/s00439-013-1279-2. Epub 2013 Mar 1.
Kawasaki disease (KD) is a dominant cause of acquired heart disease in children due to frequent complicating coronary artery lesions (CALs). Genome-wide association study and linkage analysis have recently identified 6 susceptibility loci at genome-wide significance of P < 5.0 × 10(-8) in subjects of Japanese, Taiwanese and European. In present study, we analysed the variants of 6 single nucleotide polymorphisms (SNPs) in the genetic loci to investigate their potential effect on KD susceptibility and outcomes in Han Chinese population. As a result, the risk alleles of rs1801274 and rs2254546 were observed significant effect on KD with higher frequencies in 358 patients than those in 815 controls. The significant role of rs1801274, rs2857151 and rs2254546 in KD was found in the multi-variable logistic regression analysis of the SNPs. Two 2-locus and one 3-locus combinations of the SNPs showed significant effect on KD with stronger association with KD relative to comparable single SNP or 2-locus combinations. Significant susceptibility to CALs was found in KD patients with high-risk genotypes at both rs1801274 and rs2857151. The meta-analyses first revealed significant risk for CALs in KD patients carrying risk allele of rs11340705, and the association of rs28493229 with KD was not observed in the Han Chinese. In conclusion, the findings demonstrated that 5 of the 6 genetic loci influence the risk for KD and 3 of them may be involved in secondary CALs formation in Han Chinese. The additive effects of 3 multi-locus combinations on KD/CALs imply that some loci may participate together in certain unknown gene networks related to KD/CALs. Further function studies of the genetic loci are helpful for better understanding the pathophysiology of KD.
川崎病（KD）是儿童后天性心脏病的主要病因，常并发冠状动脉病变（CALs）。全基因组关联研究和连锁分析最近在日本、中国台湾和欧洲人群中发现了 6 个易感基因座，其基因组范围内的 P < 5.0 × 10(-8)。本研究分析了 6 个单核苷酸多态性（SNPs）在遗传位点的变异，以探讨其在汉族人群中对 KD 易感性和结局的潜在影响。结果发现，rs1801274 和 rs2254546 的风险等位基因在 358 例患者中的频率明显高于 815 例对照，对 KD 有显著影响。在 SNP 的多变量逻辑回归分析中，rs1801274、rs2857151 和 rs2254546 对 KD 的作用显著。SNPs 的两个 2 位点和一个 3 位点组合对 KD 有显著影响，与单个 SNP 或 2 位点组合相比，与 KD 的相关性更强。在 rs1801274 和 rs2857151 高风险基因型的 KD 患者中发现了对 CALs 的显著易感性。荟萃分析首次显示，携带 rs11340705 风险等位基因的 KD 患者发生 CALs 的风险显著增加，而 rs28493229 与 KD 无关。总之，研究结果表明，6 个遗传位点中的 5 个影响 KD 的发病风险，其中 3 个可能与汉族人群中继发的 CALs 形成有关。3 个多基因组合对 KD/CALs 的累加效应表明，某些基因座可能共同参与与 KD/CALs 相关的某些未知基因网络。对遗传位点的进一步功能研究有助于更好地了解 KD 的病理生理学。
