Chairta Paraskevi, Nicolaou Paschalis, Christodoulou Kyproula
Neurogenetics Department, The Cyprus Institute of Neurology and Genetics, Nicosia 2370, Cyprus; Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Nicosia 2370, Cyprus.
Neurogenetics Department, The Cyprus Institute of Neurology and Genetics, Nicosia 2370, Cyprus; Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Nicosia 2370, Cyprus.
Hum Immunol. 2017 Feb;78(2):153-165. doi: 10.1016/j.humimm.2016.10.017. Epub 2016 Oct 29.
Systemic sclerosis is an autoimmune rheumatic disease characterised by fibrosis, vasculopathy and inflammation. The exact aetiology of SSc remains unknown but evidences show that various genetic factors may be involved. This review aimed to assess HLA alleles/non-HLA polymorphisms, microsatellites and chromosomal abnormalities that have thus far been associated with SSc. PubMed, Embase and Scopus databases were searched up to July 29, 2015 using a combination of search-terms. Articles retrieved were evaluated based on set exclusion and inclusion criteria. A total of 150 publications passed the filters. HLA and non-HLA studies showed that particular alleles in the HLA-DRB1, HLA-DQB1, HLA-DQA1, HLA-DPB1 genes and variants in STAT4, IRF5 and CD247 are frequently associated with SSc. Non-HLA genes analysis was performed using the PANTHER and STRING databases. PANTHER classification revealed that inflammation mediated by chemokine and cytokine, interleukin and integrin signalling pathways are among the common extracted pathways associated with SSc. STRING analysis showed that NFKB1, CSF3R, STAT4, IFNG, PRL and ILs are the main "hubs" of interaction network of the non-HLA genes associated with SSc. This study gathers data of valid genetic factors associated with SSc and discusses the possible interactions of implicated molecules.
系统性硬化症是一种自身免疫性风湿性疾病，其特征为纤维化、血管病变和炎症。系统性硬化症的确切病因尚不清楚，但有证据表明可能涉及多种遗传因素。本综述旨在评估迄今为止与系统性硬化症相关的人类白细胞抗原（HLA）等位基因/非HLA多态性、微卫星和染色体异常。截至2015年7月29日，使用组合检索词对PubMed、Embase和Scopus数据库进行了检索。根据设定的排除和纳入标准对检索到的文章进行评估。共有150篇出版物通过筛选。HLA和非HLA研究表明，HLA-DRB1、HLA-DQB1、HLA-DQA1、HLA-DPB1基因中的特定等位基因以及信号转导和转录激活因子4（STAT4）、干扰素调节因子5（IRF5）和CD247中的变体经常与系统性硬化症相关。使用PANTHER和STRING数据库进行非HLA基因分析。PANTHER分类显示，趋化因子和细胞因子介导的炎症、白细胞介素和整合素信号通路是与系统性硬化症相关的常见提取通路。STRING分析表明，核因子κB亚基1（NFKB1）、集落刺激因子3受体（CSF3R）、STAT4、干扰素γ（IFNG）、催乳素（PRL）和白细胞介素是与系统性硬化症相关的非HLA基因相互作用网络的主要“枢纽”。本研究收集了与系统性硬化症相关的有效遗传因素数据，并讨论了相关分子可能的相互作用。
