title: The role of genetics and epigenetics in the pathogenesis of systemic sclerosis.
abstract: Systemic sclerosis (SSc) is a complex autoimmune disease of unclear aetiology. A multitude of genetic studies, ranging from candidate-gene studies to genome-wide association studies, have identified a large number of genetic susceptibility factors for SSc and its clinical phenotypes, but the contribution of these factors to disease susceptibility is only modest. However, in an endeavour to explore how the environment might affect genetic susceptibility, epigenetic research into SSc is rapidly expanding. Orchestrated by environmental factors, epigenetic modifications can drive genetically predisposed individuals to develop autoimmunity, and are thought to represent the crossroads between the environment and genetics in SSc. Therefore, in addition to providing a comprehensive description of the current understanding of genetic susceptibility underlying SSc, this Review describes the involvement of epigenetic phenomena, including DNA methylation patterns, histone modifications and microRNAs, in SSc.
authors.affiliation: Department of Rheumatology &Clinical Immunology, Laboratory of Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands.
authors.forename: Jasper C A
authors.initials: JC
authors.lastname: Broen
authors.affiliation: Department of Rheumatology &Clinical Immunology, Laboratory of Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands.
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
authors.affiliation: Department of Rheumatology &Clinical Immunology, Laboratory of Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands.
authors.forename: Marzia
authors.initials: M
authors.lastname: Rossato
mesh_terms: D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006657:Histones / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000235:genetics*
chemical_list: D006657:Histones; D035683:MicroRNAs