DYSLIPIDEMIA AND HYPERGLYCEMIA IN HYPERTENSIVE PATIENTS ASSOCIATE WITH GNB3 (RS5443) AND NOS3 (RS2070744) GENES’ ALLELIC STATE

Abstract

Objective: More than 700 million people worldwide live with untreated essential arterial hypertension (EAH). The objective of the study was to evaluate the risks of metabolic disorders in EAH patients depending on guanine nucleotide-binding protein-↓3 subunit (GNB3, rs5443) and endothelial nitric oxide synthase (NOS3, rs2070744) genes’ allelic state. Design and method: The cohort case-control study involved 100 EAH patients (moderate-very high cardiovascular risks, aged 45-65 years) and 48 practically healthy (control). Metabolic disorders were evaluated by glucose blood value and lipids panel: total cholesterol (TC), triglycerides (TG), Low-, and High- density lipoprotein cholesterol (LDL-C, HDL-C) levels. The atherogenic index (AI) was calculated by the equation: (TC-HDL-C)/HDL-C. GNB3 (rs5443) and NOS3 (rs2070744) genotyping perfrmed by TaqMan probes in CFX96 Real-Time PCR Detection System. Results: Hyperglycemia (>6.1 mmol/l), hypertriglyceridemia (TG>1.7 mmol/l) and decreased HDL-C (<1.2 mmol/l) were relatively more common in EAH patients than in the control group by 36.11% (⇙2 = 17.88; p<0.001), 23.61% (⇙2 = 6.43; p = 0.011) and 25.0% (⇙2 = 8.32; p = 0.004) respectively. Therefore, the fasting hyperglycemia increases the EAH risk in the examined population ninefold [OR95%CI:2.86-27.08; p<0.001], hypertriglyceridemia and decreased HDL-C elevates the risk almost 3 and 3.5 times as well [OR95%CI:1.23-5.56; p = 0.009 and OR95%CI:1.46-8.71; p = 0.003], respectively. The risk of metabolic disorders (dyslipidemia and hyperglycemia) in EAH patients does not depend on NOS3 gene polymorphism (rs2070744). Contrary, in T-allele patients of the GNB3 gene (rs5443) prevailed subjects with elevated LDL-C (>3.0 mmol/l) over those with CC-genotype by 13.89% (p = 0.05). Other parameters of lipid metabolism and hyperglycemia did not differ significantly between GNB3 (rs5443) genes allelic state. However, the mutational T-allele of the GNB3 gene (825C>T) increases the risk of hyperlipidemia 8.5 times [OR 95%CI:0.99-72.70; p = 0.05] due to atherogenic LDL-C, with the protective role of CC-genotype [OR = 0.12; OR 95%CI:0.01-1.0; p = 0.048]. Conclusions: Fasting hyperglycemia, hypertriglyceridemia and lowered HDL-C, enhance the arterial hypertension risk 3-9 times (p<0.01). The polymorphic site of GNB3 (rs5443) gene, but not NOS3 (rs2070744) gene associate with hyperlipidemia in hypertensive patients.