Association of the structure of the glucocorticoid receptor and single nucleotide <i>NR3C1</i> gene polymorphisms with metabolic disorders

Abstract

Glucocorticoid therapy is widely used in the treatment of various pathologies. Sensitivity to glucocorticoids (GC) has a serious impact not only on the effectiveness of their action, but also on the severity of side effects, the formation of risk factors and the development of cardiovascular diseases (CVD). Variability of sensitivity to GC causes different phenotypes and severity of metabolic disorders underlying CVD. Among them, one can distinguish a decrease in muscle mass and strength, obesity, glucose and lipid metabolism impairment, and others. Glucocorticoids carry out their effects by binding to the glucocorticoid receptor (GR), and therefore this is considered a critical point in their action. This review presents data on the significance of the glucocorticoid receptor structure, examines the main single nucleotide polymorphisms (SNP) of the NR3C1 gene associated with hypersensitivity or relative resistance to glucocorticoids in the context of metabolic disorders and the development of CVD. The association of the four most studied SNP of the GR gene with metabolic risks is described in detail: BclI (rs41423247), N363S (rs56149945), ER22/23EK (rs6189/rs6190), GR-9ß (rs6198). Their determination can contribute to clarifying the prognosis of both the effectiveness of GC and the development of metabolic disorders, and subsequent early correction of CVD risk factors.