ENDOTHELIAL NITRIC OXIDE SYNTHASE (NOS3) AND GUANINE NUCLEOTIDE-BINDING PROTEIN (GNB3) GENES’ POLYMORPHISMS PORTEND OBESITY IN HYPERTENSIVE PATIENTS: THE GENDER ASPECT

Abstract

Objective: Obesity is a major risk factor of essential arterial hypertension (EAH) because of neuro-hormonal, sympathoadrenal and renin-angiotensin-aldosterone system activation, as well as endothelial dysfunction and systemic low grade inflammation. However, genetic mechanisms of obesity development in EAH patients remained unclear. Therefore, we studied the guanine nucleotide-binding protein-↓3 (GNB3, rs5443) and endothelial nitric oxide synthase (NOS3, rs2070744) genes’ polymorphisms as possible genetic harbingers of obesity in EAH patients particularly focusing on gender. Design and method: One-hundred EAH patients with hypertensive-mediated organ damage (moderate-very high cardiovascular risks, aged 45-65 years) and 48 practically healthy (control) participated in the cohort case-control study. Obesity was determined by body mass index (BMI) >30 kg/m2. GNB3 (rs5443) and NOS3 (rs2070744) genotyping performed by TaqMan probes (CFX96 Real-Time PCR). Results: The NOS3 gene mutation in the homozygous state occurs in 16.67% of EAH patients and for the GNB3 gene in 8.33% of cases, which does not differ from the control group. The relative frequency of obese prevailed among EAH patients with the mutated C-allele carriers of the NOS3 gene by 31.94% (⇙2 = 13.58; p<0.001) and T-allele of the GNB3 gene (30.56%) in the absence of such among healthy control. The risk of obesity increases in EAH patients in C-allele carriers of the NOS3 gene almost 6 times [OR 95%CI:2.11-14.82; p<0.001] and in T-allele patients of the GNB3 gene – more than 10 times [OR 95%CI:2.25-45.44; p<0.001], 1.3 times more often in women than men (p<0,05), regardless the genes’ allelic state. The TT-genotype of the NOS3 gene and the CC-genotype of the GNB3 gene play a protective role against obesity. Conclusions: The C-allele of the NOS3 gene (rs2070744) and the T-allele of the GNB3 gene (rs5443) increase the obesity risk in hypertensive patients 6-10 fold (p<0.001) as well, 1.3 times more often in women, than men.