Estudio de regiones génicas relacionadas con el estrés oxidativopapel en la artrosis

Abstract

Osteoarthritis is the most prevalent and incapacitating rheumatic disease worldwide and currently there isn’t any effective treatment for it. Initially, it manifests itself at the molecular level, generating anatomical and / or physiological alterations. The role of epigenetics is crucial to understand the gene-environment interaction in complex diseases, and recently, different patterns of methylation have been linked to osteoarthritis. On the other hand, mitochondria has played an important role because of its importance in cell detoxification and mitochondrial haplogroups have been shown to influence the predisposition and progression of the disease. This study has focused on the search for new genetic regions related to oxidative stress with potential value as therapeutic targets or disease biomarkers and independent of the affected joint. To do this, experiments on gene expression, methylome analysis and sequencing have been carried out together with association studies and functional in vitro experiments with chondrocytes to identify new targets. The results obtained have identified genes implicated in oxidative stress as potential therapeutic targets, distinctive methylation profiles between mitochondrial haplogroups, differential expression of the transcriptome in the disease and the interaction of mitochondrial clusters with nuclear polymorphisms and their functional consequences.