| Fecha: |
2021 |
| Resumen: |
Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune populatio. |
| Ayudas: |
Ministerio de Economía y Competitividad FJCI_2014_20652
European Commission. Horizon 2020 806975
|
| Derechos: |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Lengua: |
Anglès |
| Documento: |
Article ; recerca ; Versió publicada |
| Materia: |
Autoantibodies ;
DNA Methylation ;
Epigenomics ;
Female ;
Gene Expression ;
Gene Expression Regulation ;
Genetic Variation ;
HLA Antigens ;
Humans ;
Interferons ;
Male ;
Sjogren's Syndrome |
| Publicado en: |
Scientific reports, Vol. 11 Núm. 1 (december 2021) , p. 23292, ISSN 2045-2322 |
visitante ::
identificación
(Consejo Superior de Investigaciones Científicas)
