Identification of novel susceptibility genes in childhood-onset systemic lupus erythematosus using a uniquely designed candidate gene pathway platform
Identification of novel susceptibility genes in childhood-onset systemic lupus erythematosus using a uniquely designed candidate gene pathway platform
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DOI：
10.1002/art.23060
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发表时间：
2007-12-01
影响因子：
--
通讯作者：
Zidovetzki, Raphael
中科院分区：
文献类型：
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作者：
Jacob, Chaim O.;Reiff, Andreas;Zidovetzki, Raphael
Objective.儿童期发病的系统性红斑狼疮（SLE）是一个独特的遗传学研究的患者亚群。本研究采用一种新的候选基因通路微阵列平台，对儿童期SLE患者及其父母的基因表达进行研究，以确定SLE易感基因。利用生物信息学工具，设计并验证了来自1，204个基因的9，412个单核苷酸多态性（SNP）的平台。分子倒置探针和高通量SNP技术用于测定开发。753例受试者，对应于251个完整的儿童期发病的SLE家系，采用传递不平衡检验（TDT）和多重检验校正进行基因分型和分析。基于家族的TDT显示SLE与P-选择素基因（SELP）的N673 S多态性（P = 5.74 × 10（-6））和白细胞介素-1受体相关激酶1基因（IRAK 1）的C203 S多态性（P = 9.58 × 10（-6））显著相关。这2个SNP具有95%概率的多重检验校正的错误发现率，被认为是已证实的。此外，7个额外的SNP显示q值为
Objective. Childhood-onset systemic lupus erythematosus (SLE) presents a unique subgroup of patients for genetic study. The present study was undertaken to identify susceptibility genes contributing to SLE, using a novel candidate gene pathway microarray platform to investigate gene expression in patients with childhood-onset SLE and both of their parents.Methods. Utilizing bioinformatic tools, a platform of 9,412 single-nucleotide polymorphisms (SNPs) from 1,204 genes was designed and validated. Molecular inversion probes and high-throughput SNP technologies were used for assay development. Seven hundred fifty three subjects, corresponding to 251 full trios of childhood-onset SLE families, were genotyped and analyzed using transmission disequilibrium testing (TDT) and multitest corrections.Results. Family-based TDT showed a significant association of SLE with a N673S polymorphism in the P-selectin gene (SELP) (P = 5.74 X 10(-6)) and a C203S polymorphism in the interleukin-1 receptor-associated kinase 1 gene (IRAK1) (P = 9.58 X 10(-6)). These 2 SNPs had a false discovery rate for multitest correction of 95% probability of being considered as proven. Furthermore, 7 additional SNPs showed q values of