The clinical significance of the glucocorticoid receptors: Genetics and epigenetics

•The glucocorticoid receptor (GR) regulates a wide range of gene networks involved in stress response, inflammation, and metabolism.•The polymorphisms of GR gene play a major role in cellular responses to GCs and associates with different diseases.•A prolonged exposure to GCs levels in early life, depression and/or stress can trigger epigenetic changes at the GR gene.•The expression of GR can be effected by genetic polymorphisms and epigenetic alteration in its gene. The impacts of glucocorticoids (GCs) are mainly mediated by a nuclear receptor (GR) existing in almost every tissue. The GR regulates a wide range of physiological functions, including inflammation, cell metabolism, and differentiation playing a major role in cellular responses to GCs and stress. Therefore, the dysregulation or disruption of GR can cause deficiencies in the adaptation to stress and the preservation of homeostasis. The number of GR polymorphisms associated with different diseases has been mounting per year. Tackling these clinical complications obliges a comprehensive understanding of the molecular network action of GCs at the level of the GR structure and its signaling pathways. Beyond genetic variation in the GR gene, epigenetic changes can enhance our understanding of causal factors involved in the development of diseases and identifying biomarkers. In this review, we highlight the relationships of GC receptor gene polymorphisms and epigenetics with different diseases.