Genomic and genetic studies of systemic sclerosis: A systematic review

Abstract

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 STRING₁₀ 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. STRING₁₀ 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.

Keywords: Autoimmune disease; Genetics; Scleroderma; Systematic review; Systemic sclerosis.