LINKAGE BETWEEN NOS3 (RS2070744) AND GNB3 (RS5443) GENES’ POLYMORPHISM, CAROTID ARTERIES STRUCTURAL CHANGES AND ENDOTHELIAL DYSFUNCTION IN ESSENTIAL HYPERTENSION

Abstract

Objective: This study aims to verify the risk of endothelial dysfunction (ED) and carotid intima media thickness (IMT) changes depending on GNB3 (rs5443) and NOS3 (rs2070744) genes’ polymorphism in essential arterial hypertensives (EAH). Design and method: One-hundred EAH patients (moderate-very high cardiovascular risks, aged 45–65 years) and 48 practically healthy (control) participated in the case-control study. Soluble Vascular Cell Adhesion Molecule (sVCAM-1), total NO metabolites, transcriptional activity of NOS3 gene, Endothelium-Dependent Flow-Mediated Dilation of the Brachial Artery (FMD BA) and carotid IMT were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping performed by TaqMan probes (CFx96ÔReal-Time PCR). Results: C-allele of NOS3 gene elevates the risk of atherosclerotic plaques on the carotid arteries over 3.5 times [OR95%CI:1.24–11.20; p = 0.019 and OR95%CI:1.22–10.18; p = 0.018], ED – by total NO metabolites decrease (<25 mol/l) and sVCAM-1 value raise (>1050 ng/ml) – 12 and 4 times [OR95%CI:1.23–112.7; p = 0.023 and OR95%CI:1.24–11.20; p = 0.019], respectively. Moreover, C-allele of NOS3 gene heighten the low NOS3 gene expression probability 69 times [OR95%CI:17,72–520,0; p < 0,001]. The minor T-allele of GNB3 gene increases the risk of carotid arteries structural changes: by IMT (>0,9 mm) – 3 times [OR95%CI:1.09–7.74; p = 0.027], atherosclerotic plaques – 10 and 5 times [OR95%CI:2.55–38.0; p < 0.001 and OR95%CI:1.61–13.27; p = 0.003]. Besides, the T-allele of GNB3 gene enhances the high sVCAM-1 levels probability over 3 times [OR95%CI:1.06–9.59; p = 0.032]. Moderate and severe ED grades increase the risk of severe EAH 3 and 5.5 times [OR95%CI:1.13–9.34; p = 0.025 and OR95%CI:1.96–14.45; p < 0.001]. The severe EAH course risk is associated more with the structural changes of the carotid arteries (IMT > 0,9 mm increases the likelihood 3.5 times (p = 0.012), atherosclerotic plaques – 4 and 3.5 times (p < 0,05) and decreased NOS3 gene expression – 3 times (p = 0.042), but not depend on separate ED markers (FMD BA, total NO metabolites or sVCAM-1). Conclusions: ED enhance the risk of severe EAH course 3–5.5 times. c-allele of NOS3 gene elevates the risk of both structural changes of the carotid arteries 3.5 times and particularly ED – 4–69 times. T-allele of GNB3 gene increases the risk of the carotid arteries structural changes more than ED – 3.5–4 vs 3 times as well.