Genetics of systemic sclerosis

Abstract

Genetic epidemiology suggests that the molecular background of systemic sclerosis (SSc) such as autoantibody production or gene expression profiles may be highly hereditary; however, the clinical occurrence of SSc may require non-hereditary factor(s). Genome-wide association studies (GWASs) confirmed that the HLA genes are the strongest genetic factors, although specific risk alleles are different among populations and among the clinical subsets such as those determined by autoantibody profiles. GWAS and candidate gene studies revealed more than a dozen of convincing candidate genes; however, thus far, all of them are shared by other diseases and do not appear to explain the unique features of SSc such as extensive fibrosis and vascular damage. Thus, something must be missing, and more studies are required to reveal the secrets of this enigmatic disease. Here, we reviewed the genetic studies of SSc, with emphasis on those performed on Asian populations.