Objective. To search for polygenic interactions associated with left ventricular hypertrophy (LVH) in patients with arterial hypertension (AH).

Materials and methods. The study included 237 patients (130 men and 107 women), average age was 48.1±11.3 years. An associative analysis of the gene polymorphism of the angiotensin converting enzyme ACE (I/D), angiotensinogen AGT (M235T), receptors for angiotensin II type 1 AGTR1 (A1166C) and type 2 AGTR2 (C3123A), aldosterone synthase CYP11B2 (C(-344)T), renin REN (19-83 G/A), methylenetetrahydrofolate reductase MTHFR (C677T), endothelial synthase NOS3 (E298D), type 2 bradykinin receptors BDKR2 (T58C) with echocardiographic signs of LVH was performed in patients with hypertension. The search for polygenic associations was performed using APSampler software.

Results. The differences were obtained for biallele combinations of mutant C allele AGTR1(A1166C) and T allele CYP11B2 (C344T) (OR=1.95; 95% CI=1.35—2.81; p=0.001); C allele AGTR1 (A1166C) and T allele MTHFR (C677T) (OR=2.53; 95% CI=1.49-4.30; p=0.013); T allele AGT (M235T) and D allele NOS3(E298D) (OR=2.67; 95% CI=1.91-3.74; p=0.004) which associated with an increased risk of LVH in patients with hypertension. In case of сombination of three mutant alleles of polymorphic loci AGT (M235T), NOS3 (E298D) and CYP11B2 (C344T) the LVH development increased by 3.6 times (OR=3.56; 95% CI=2.08-6.08; p=0.001). In the logistic regression model, age, abdominal obesity, the presence of mutant bi- and triallelic combinations of polymorphic loci AGTR1 (A1166C) with MTHFR (C677T) and AGT (M235T) with NOS3 (E298D), CYP11B2 (C344T) were independent factors of increased susceptibility to LVH development.

Conclusion. This study revealed the epistatic effect of the studied polymorphic loci of the genes of the renin-angiotensin-aldosterone, endothelial, and homocysteine systems associated with LVH. Abdominal obesity and age enhance the effect of a genetic predisposition to LVH in patients with hypertension.

Ключевые слова: , , , , , , ,
Автор(ы): O. S. Pavlova, N. V. Zatoloka, S. E. Ogurtsova, Y. V. Shrub, V. I. Malugin, A. G. Mrochek