Systemic Sclerosis is a Complex Disease Associated Mainly with Immune Regulatory and Inflammatory Genes
Jingxiao Jin 1, 2, §, Chou Chou 1, Maria Lima 1, 3, Danielle Zhou 1, 4, Xiaodong Zhou*, 1
Identifiers and Pagination:Year: 2014
First Page: 29
Last Page: 42
Publisher Id: TORJ-8-29
Article History:Received Date: 15/5/2014
Revision Received Date: 4/8/2014
Acceptance Date: 7/8/2014
Electronic publication date: 29 /9/2014
Collection year: 2014
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
Systemic sclerosis (SSc) is a fibrotic and autoimmune disease characterized clinically by skin and internal organ fibrosis and vascular damage, and serologically by the presence of circulating autoantibodies. Although etiopathogenesis is not yet well understood, the results of numerous genetic association studies support genetic contributions as an important factor to SSc. In this paper, the major genes of SSc are reviewed. The most recent genome-wide association studies (GWAS) are taken into account along with robust candidate gene studies. The literature search was performed on genetic association studies of SSc in PubMed between January 2000 and March 2014 while eligible studies generally had over 600 total participants with replication. A few genetic association studies with related functional changes in SSc patients were also included. A total of forty seven genes or specific genetic regions were reported to be associated with SSc, although some are controversial. These genes include HLA genes, STAT4, CD247, TBX21, PTPN22, TNFSF4, IL23R, IL2RA, IL-21, SCHIP1/IL12A, CD226, BANK1, C8orf13-BLK, PLD4, TLR-2, NLRP1, ATG5, IRF5, IRF8, TNFAIP3, IRAK1, NFKB1, TNIP1, FAS, MIF, HGF, OPN, IL-6, CXCL8, CCR6, CTGF, ITGAM, CAV1, MECP2, SOX5, JAZF1, DNASEIL3, XRCC1, XRCC4, PXK, CSK, GRB10, NOTCH4, RHOB, KIAA0319, PSD3 and PSOR1C1. These genes encode proteins mainly involved in immune regulation and inflammation, and some of them function in transcription, kinase activity, DNA cleavage and repair. The discovery of various SSc-associated genes is important in understanding the genetics of SSc and potential pathogenesis that contribute to the development of this disease.