Association of glucocorticoid receptor gene NR3C1 genetic variants with angiographically documented coronary artery disease and its risk factors

Background and aims: Glucocorticoids and their receptors are involved in inflammation and many cardiovascular risk factors. We examined associations of Tth111I, N363S and ER22/23EK NR3C1 gene polymorphisms and haplotypes, with coronary artery disease (CAD), severity of CAD (single-vessel vs. multivessel disease) and risk factors.

Methods: Three hundred ten individuals were submitted to coronary angiography. Selected genotypes were determined by PCR-RFLP.

Results: Carriers of the Tth111I allele T were found significantly less often in the CAD compared with the non-CAD group (49.7 vs. 64.6%, p = 0.013); this association was similar for TGA haplotype carriers (49.2 vs. 62.8%, p = 0.024); the T allele was more frequent in females (66.3 vs. 51.1%, p = 0.020) and its presence was associated with higher levels of HDL-cholesterol (46.6 ± 12.7 vs. 43.5 ± 10.1 mg/dL for T-carriers vs. noncarriers, p = 0.045). The TT genotype proved to be less common in MVD than SVD (5.9 vs. 14.1%, p = 0.075). The 363S allele was significantly associated with diabetes mellitus (DM) (24.4 vs. 10.9%; carriers in DM and non-DM subjects, respectively, p = 0.027), the TT genotype or TGA/TGA diplotype (in which the 363S allele was absent) were less frequent in DM than in non-DM subjects (p = 0.012 for Tth111I-TT and p = 0.020 for TGA/TGA diplotype). No significant associations between CAD and N363S or ER22/23EK polymorphisms were found.

Conclusions: Our results suggest that the Tth111I NR3C1 polymorphism may play a protective role in the development of CAD, and homozygous TT in development of MVD. The N363S polymorphisms may contribute to the development of diabetes in the Polish population.