High-density genotyping of immune loci in Kawasaki disease and IVIG treatment response in European-American case-parent trio study.
High-density genotyping of immune loci in Kawasaki disease and IVIG treatment response in European-American case-parent trio study.
复制标题
DOI：
10.1038/gene.2014.47
复制
发表时间：
2014-12
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
作者：
川崎（KD）是一种弥漫性急性小血管炎，见于儿童，具有遗传和自身免疫因素。我们使用免疫芯片阵列对112例欧洲血统（经AIMS证实）的病例-父母三人组进行基因分型，并对KD和IVIG无应答的易感性进行关联分析。KD易感性采用传递不平衡检验进行评估，而IVIG无应答采用多变量logistic回归分析进行评估。我们复制了三个基因区域（FCGR，CD 40/CDH 22和HLA-DQB 2/HLA-DOB）中的SNP，这些区域先前与KD相关，并为其他发现的几个新的SNP提供了支持，这些SNP在KD发病机制中具有潜在的通路。FUT 1基因3′ UTR的rs 838143（2.7×10-5）和LOC 730109的BRD 7 P2基因间区的rs 9847915（6.81×10-7）分别是加性和显性模型中KD易感性的最高位点。在加性和显性模型中，IVIG反应性的最高命中分别是BAZ 1A基因组C14 orf 19基因间区的rs 1200332（1.4×10-4）和STX 1B基因内含子的rs 4889606（6.95×10-5）。我们的研究表明，自身免疫性疾病的基因和生物学通路在KD的发病机制和IVIG反应机制中起着重要作用。
Kawasaki disease (KD) is a diffuse and acute small-vessel vasculitis observed in children and has genetic and autoimmune components. We genotyped 112 case-parent trios of European decent (confirmed by AIMS) using the ImmunoChip array and performed association analyses with susceptibility to KD and IVIG non-response. KD susceptibility was assessed using the transmission disequilibrium test whereas IVIG non-response was evaluated using multivariable logistic regression analysis. We replicated SNPs in three gene regions (FCGR, CD40/CDH22, and HLA-DQB2/HLA-DOB) that have been previously associated with KD and provide support to other findings of several novel SNPs in genes with potential pathway in KD pathogenesis. SNP rs838143 in the 3′ UTR of FUT1 gene (2.7×10-5) and rs9847915 in the intergenic region of LOC730109 ∣ BRD7P2 (6.81×10-7) were the top hits for KD susceptibility in additive and dominant models, respectively. The top hits for IVIG responsiveness were rs1200332 in the intergenic region of BAZ1A ∣ C14orf19 (1.4×10-4) and rs4889606 in the intron of the STX1B gene (6.95×10-5) in additive and dominant models, respectively. Our study suggests that genes and biological pathways involved in autoimmune diseases play an important role in the pathogenesis of KD and IVIG response mechanism.