title: 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.
authors.affiliation: Department of Biomedicine, Division of Rheumatology, University of Florence, AOUC, Florence, Italy. eloisaromano@libero.it
authors.forename: Eloisa
authors.initials: E
authors.lastname: Romano
authors.forename: Mirko
authors.initials: M
authors.lastname: Manetti
authors.forename: Serena
authors.initials: S
authors.lastname: Guiducci
authors.forename: Claudia
authors.initials: C
authors.lastname: Ceccarelli
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
mesh_terms: D015551:Autoimmunity / Q000235:genetics*; D002874:Chromosome Mapping; D015331:Cohort Studies; D004843:Epistasis, Genetic; D005355:Fibrosis; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D015201:Meta-Analysis as Topic; D055806:Microvessels / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012595:Scleroderma, Systemic / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D014652:Vascular Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
chemical_list: D006680:HLA Antigens