Influence of genetic factors on the development of target organ lesions in relation to age in diagnosis of arterial hypertension

Abstract To analyze the impact of polymorphism of a group of genes encoding for endothelial function on the development of target organ lesions in arterial hypertension (AH) in relation to age. Six hundred and seventy-two AH patients (mean age 50.6 years; men 67%) were examined. Microalbuminuria (MAU) was estimated. Electrocardiography, echocardiography, and carotid ultrasonography were performed. A control group comprised 184 subjects. Single-nucleotide substitutions genotyping of the Glu298Asp endothelial NO synthase (eNOS), p22phox of NADPH oxidase subunit C242T, and angiotensin II type 1 receptor (ATR1) A1166C gene polymorphisms was conducted by a polymerase chain reaction (PCR) via restriction fragment length polymorphism analysis, and M235T substitution genotyping of the G-6A polymorphism of the angiotensinogen gene was performed by a real-time allele-specific PCR. The impact of the polymorphisms on the development of MAU, left ventricular hypertrophy (LVH), carotid lesion was analyzed in the groups: AH was diagnosed in subjects aged less than 35 years (n = 128) or older. The ultrasound signs of carotid lesion, LVH, and MAU were revealed in 65, 39, and 10.5% of the patients with AH, respectively. The subgroups showed differences in the distribution of polymorphisms of the study genes in relation to age at AH detection. In patients with AH diagnosed at less than 35 years of age, pathological changes in the carotid are associated with a G allele of the Glu298Asp eNOS polymorphism (odds ratio (OR) = 2.3; p = 0.016) and with an T allele of the p22phox of NADPH oxidase subunit C242T polymorphism (OR 1.7; p = 0.049). In this age subgroup, LVH was associated with an A allele of the Glu298Asp eNOS polymorphism (OR = 1.9; p = 0.037), MAU was with an A allele of the Glu298Asp eNOS polymorphism (OR = 3.6; p = 0.02) and a C allele of the ATR1 A1166C gene polymorphism (OR = 2.6; p = 0.034).