Genetic variants in the glucocorticoid receptor gene (NR3C1) and cardiovascular disease risk. The Leiden 85-plus Study.

Recently, the ER22/23EK, N363S and BclI polymorphisms in the glucocorticoid receptor (GR) gene have been linked to altered cortisol sensitivity and to cortisol-associated disorders. The aim of this study was to investigate the effect of these genetic variants in the GR gene on cardiovascular disease and mortality in elderly persons aged 85 years and over. In the population-based Leiden 85-plus Study, 552 participants were genotyped for the ER22/23EK, N363S and BclI polymorphisms, and the effects of the polymorphisms on metabolic profile, body composition, and on the prevalence of cardiovascular pathologies at baseline, were assessed. Allcause and cardiovascular disease mortality risks dependent on the SNPs were calculated after a 4.2-year follow-up. The analyses of metabolic profile revealed that carriers of the ER22/23EK polymorphism have higher HbA1C levels (P<0.001) and carriers of the N363S SNP have higher LDL cholesterol (P<0.001) and triglyceride concentrations (P=0.03), compared to the non-carriers. The only significant association between genotype and body composition analyses was for height and the ER22/23EK polymorphism. Men carrying the ER22/23EK polymorphism were taller (P=0.02) compared to non-carriers. No associations with cardiovascular pathologies, allcause and cardiovascular mortality were observed for any of the polymorphisms. We conclude that, in spite the effect of the ER22/23EK and N363S SNPs on metabolism, these polymorphisms together with the BclI SNP, do not affect the risks of cardiovascular disease and survival at old age.