Integrative epigenomics in Sjogren ' s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature
Por:
Teruel, M, Barturen, G, Martinez-Bueno, M, Castellini-Perez, O, Barroso-Gil, M, Povedano, E, Kerick, M, Catala-Moll, F, Makowska, Z, Buttgereit, A, Pers, JO, Maranon, C, Ballestar, E, Martin, J, Carnero-Montoro, E and Alarcon-Riquelme, ME
Publicada:
2 dic 2021
Resumen:
Primary Sjogren'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 population.
Filiaciones:
Teruel, M:
Univ Granada, GENYO, Ctr Genom & Oncol Res Pfizer, Andalusian Reg Govt, Granada 18016, Spain
Barturen, G:
Univ Granada, GENYO, Ctr Genom & Oncol Res Pfizer, Andalusian Reg Govt, Granada 18016, Spain
Martinez-Bueno, M:
Univ Granada, GENYO, Ctr Genom & Oncol Res Pfizer, Andalusian Reg Govt, Granada 18016, Spain
Castellini-Perez, O:
Univ Granada, GENYO, Ctr Genom & Oncol Res Pfizer, Andalusian Reg Govt, Granada 18016, Spain
Barroso-Gil, M:
Univ Granada, GENYO, Ctr Genom & Oncol Res Pfizer, Andalusian Reg Govt, Granada 18016, Spain
Povedano, E:
Univ Granada, GENYO, Ctr Genom & Oncol Res Pfizer, Andalusian Reg Govt, Granada 18016, Spain
Kerick, M:
IPBLN CSIC, Inst Parasitol Biomed Lopez Neyra, Consejo Super Invest Cient, Granada 18016, Spain
Catala-Moll, F:
Josep Carreras Res Inst IJC, Epigenet & Immune Dis Grp, Barcelona 08916, Spain
LHosp Llobregat, IDIBELL, Bellvitge Biomed Res Inst, Barcelona, Spain
Makowska, Z:
Bayer Pharma Aktiengesellschaft, Pharmaceuticals Div, Berlin, Germany
Buttgereit, A:
Bayer Pharma Aktiengesellschaft, Pharmaceuticals Div, Berlin, Germany
Pers, JO:
Univ Brest, CHU Brest, INSERM, Labex IGO, Brest, France
Maranon, C:
Univ Granada, GENYO, Ctr Genom & Oncol Res Pfizer, Andalusian Reg Govt, Granada 18016, Spain
:
Josep Carreras Res Inst IJC, Epigenet & Immune Dis Grp, Barcelona 08916, Spain
LHosp Llobregat, IDIBELL, Bellvitge Biomed Res Inst, Barcelona, Spain
Martin, J:
IPBLN CSIC, Inst Parasitol Biomed Lopez Neyra, Consejo Super Invest Cient, Granada 18016, Spain
Carnero-Montoro, E:
Univ Granada, GENYO, Ctr Genom & Oncol Res Pfizer, Andalusian Reg Govt, Granada 18016, Spain
Alarcon-Riquelme, ME:
Univ Granada, GENYO, Ctr Genom & Oncol Res Pfizer, Andalusian Reg Govt, Granada 18016, Spain
Karolinska Inst, Inst Environm Med, S-17167 Solna, Sweden
Green Accepted, gold, Green Published
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