Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease characterized by a wide spectrum of glandular and extra-glandular features. Genetic and epigenetic factors play an important role in the disease susceptibility and phenotype. There are a multitude of genes that have been identified as implicated in the pathogenesis of pSS, both in HLA and extra-HLA regions with a strong contribution given by genes in interferon signalling pathways. Among the HLA alleles, the most consistent associations have been found with DR2 and DR3 alleles at the DRB1 locus. Moreover, several gene variants outside the MHC locus are in genes involved in NF-κB signalling, B- and T-cell function and methylation processes possibly responsible for lymphomagenesis. There is still a lack of knowledge on precise genetic patterns and prediction models of diseases, and data on pharmacogenetics is scarce. A comprehensive summary of the common genetic factors and an extensive analysis of novel epigenetic aspects is provided, together with a view on the relationships between novel therapeutic agents for pSS and genetic targets in signalling pathways, aiming at improving tailored treatment strategies in the view of a more personalized medicine.
Keywords: Autoimmune disease; Epigenetic; Genetic; HLA; Interferon; Primary Sjögren's syndrome; RNA.
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