Genetics, Epigenetics, and Genomics of Systemic Sclerosis

Systemic sclerosis (SSc) is a complex autoimmune disease that occurs in a genetically susceptible host. Genetic studies performed so far reveal that multiple genetic loci contribute to disease susceptibility in SSc. The purpose of this review is to discuss the current knowledge of genetics in SSc by exploring the observational evidence, the different genetic studies, and their modalities as well as the most relevant genes discovered by these. The importance of gene expression variation and the different mechanisms that govern it, including the recently discovered field of epigenetics, are also explored, with an emphasis on microRNA.

Key points

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Multiple genes are associated with susceptibility to systemic sclerosis and can lead to alterations in innate and adaptive immunity, cell signaling, extracellular matrix, DNA or RNA degradation, and apoptosis or autophagy.
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There are several mechanisms (such as epigenetics and splicing mutations) that influence gene expression and are important for disease in addition to the genetic variants.
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Epigenetic mechanisms govern gene expression at different levels before translation. They are just being explored in systemic sclerosis and may help explain some of the missing heritability.