The genetics of systemic sclerosis: an update

Abstract

Systemic sclerosis (SSc) is a complex systemic disease characterised by fibrosis of the skin and internal organs, vasculopathy, and activation of the immune system. The complex pathophysiology of SSc implies the potential involvement of 'culprit' genes, either individually or, more likely, together, in driving the disease process. Most of the studies that have provided evidence for the contribution of various genes/loci in SSc pathogenesis are based on a candidate gene approach, on the basis of a shared autoimmune genetic background with other autoimmune diseases, such as systemic lupus erythematosus. In fact, autoimmune genes seem to play a pivotal role in SSc pathogenesis, while less is known about the genetic involvement in vasculopathy and fibrosis. Recently, the availability of genome-wide association studies, which make it possible to screen single-nucleotide polymorphisms across the entire genome without previous knowledge of candidate regions or genes, has yielded a wealth of new genetic susceptibility loci leading to the identification of new pathogenetic mechanisms of complex genetic disorders. In this article, we aim to provide a comprehensive review of recent studies on the genetics of SSc, including genes associated with autoimmunity, fibrosis, and vascular disease. We also discuss the most relevant data obtained in genetic association studies of large populations that included a replication strategy, or studies for which independent replication was available.