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麻疹可导致类风湿性关节炎:基于全基因组关联研究的途径和网络分析的证据。

Measles contributes to rheumatoid arthritis: evidence from pathway and network analyses of genome-wide association studies.

机构信息

Institute of Neurology, Guangdong Medical College, Zhanjiang, China ; Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.

出版信息

PLoS One. 2013 Oct 18;8(10):e75951. doi: 10.1371/journal.pone.0075951. eCollection 2013.

Abstract

Growing evidence from epidemiological studies indicates the association between rheumatoid arthritis (RA) and measles. However, the exact mechanism for this association is still unclear now. We consider that the strong association between both diseases may be caused by shared genetic pathways. We performed a pathway analysis of large-scale RA genome-wide association studies (GWAS) dataset with 5,539 cases and 20,169 controls of European descent. Meanwhile, we evaluated our findings using previously identified RA loci, protein-protein interaction network and previous results from pathway analysis of RA and other autoimmune diseases GWAS. We confirmed four pathways including Cytokine-cytokine receptor interaction, Jak-STAT signaling, T cell receptor signaling and Cell adhesion molecules. Meanwhile, we highlighted for the first time the involvement of Measles and Intestinal immune network for IgA production pathways in RA. Our results may explain the strong association between RA and measles, which may be caused by the shared genetic pathway. We believe that our results will be helpful for future genetic studies in RA pathogenesis and may significantly assist in the development of therapeutic strategies.

摘要

越来越多的流行病学研究证据表明类风湿关节炎(RA)与麻疹之间存在关联。然而,这种关联的确切机制尚不清楚。我们认为这两种疾病之间的强相关性可能是由共同的遗传途径引起的。我们对欧洲血统的 5539 例病例和 20169 例对照的大规模 RA 全基因组关联研究(GWAS)数据集进行了途径分析。同时,我们使用先前确定的 RA 基因座、蛋白质-蛋白质相互作用网络以及先前对 RA 和其他自身免疫性疾病 GWAS 的途径分析结果来评估我们的发现。我们证实了包括细胞因子-细胞因子受体相互作用、Jak-STAT 信号转导、T 细胞受体信号转导和细胞黏附分子在内的四个途径。同时,我们首次强调了麻疹和 IgA 产生途径的肠道免疫网络在 RA 中的作用。我们的研究结果可能解释了 RA 和麻疹之间的强相关性,这可能是由共同的遗传途径引起的。我们相信我们的研究结果将有助于未来对 RA 发病机制的遗传研究,并可能对治疗策略的制定有重要帮助。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec24/3799991/78c9d82cdaab/pone.0075951.g001.jpg

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