Department of Fisheries, Faculty of Animal Sciences and Fisheries, Sari Agricultural and Natural Resources University, Sari, Iran.
Department of Animal Science, Faculty of Agriculture, University of Jiroft, Jiroft, Iran.
Gene. 2019 Jul 20;706:181-187. doi: 10.1016/j.gene.2019.05.004. Epub 2019 May 11.
Systemic lupus erythematous (SEL) is a heterogeneous, systemic autoimmune disorder which is defined by its autoantibody pattern. Transcriptomic data analysis has shown pathways and immune system responses associated with SLE. Eight up-regulated genes (SOCE, MMP9, CXCL8, JUN, IL1B, NFKBIA, TNF and FOS) have been examined with four interactions among different pathways. These genes are associated with SNPs which have been identified through two datasets from SLE genome-wide association studies (GWAS). In this investigation, the GWAS results were integrated with pathway analysis of transcriptomes and several genes were detected with known SLE-related variations (TYK2, C5, SH2B, IRF5, IL2RA, STAT4, FCGR2A, IL7R, LYN, HLA-DRB and TNFAIP3). Pathway-based analysis on the Wikipathway Human Collection allowed the identification of prioritized variants in the relevant pathways, such as thymic stromal lymphopoietin (TSLP) signaling pathway linked to LYN, IL7R, STAT4 and rs7574865. Analysis of existing transcriptomes and GWAS data identified eight up-regulated candidate genes with more than four relationships among the different pathways associated with SNPs to pinpoint the relevant loci linked to SLE. The results of this investigation have expanded the number of candidate genes related to SLE and have highlighted possible pathways and GWAS-based methods for gene detection. Identification of the fundamental genes would assist in revealing the mechanisms responsible for SLE.
系统性红斑狼疮（SEL）是一种异质性、系统性自身免疫性疾病，其特征为自身抗体模式。转录组数据分析已经显示出与 SLE 相关的途径和免疫系统反应。已经检查了八个上调基因（SOC、MMP9、CXCL8、JUN、IL1B、NFKBIA、TNF 和 FOS），并发现了不同途径之间的四个相互作用。这些基因与通过 SLE 全基因组关联研究（GWAS）的两个数据集确定的 SNP 相关。在这项研究中，将 GWAS 结果与转录组途径分析相结合，并检测到几个具有已知 SLE 相关变异的基因（TYK2、C5、SH2B、IRF5、IL2RA、STAT4、FCGR2A、IL7R、LYN、HLA-DRB 和 TNFAIP3）。在 Wikipathway 人类收藏中的基于途径的分析允许确定相关途径中的优先变体，例如与 LYN、IL7R、STAT4 和 rs7574865 相关的胸苷基质淋系opoietin（TSLP）信号通路。对现有转录组和 GWAS 数据的分析确定了八个上调的候选基因，这些基因在与 SNP 相关的不同途径之间有超过四个关系，以确定与 SLE 相关的相关基因座。这项研究的结果扩展了与 SLE 相关的候选基因数量，并强调了可能的途径和基于 GWAS 的基因检测方法。鉴定基本基因将有助于揭示 SLE 相关的机制。
