Genetic approaches in the choice of therapy for hypertension in the population of Mountain Shoria

Abstract

Objective. To determine the prognostic role of the polymorphism of candidate genes for hypertension (HTN) in the effectiveness of antihypertensive therapy in the population of Mountain Shoria, taking into account the ethnic factor. Design and methods. The material for the study was the population of indigenous (Shors) and nonindigenous inhabitants of Mountain Shoria. In the first stage of the study (2013–2017), 901 indigenous people and 508 non-indigenous people were included in the continuous method. A group of patients with HTN was identified — 367 (40,7 %) shors and 230 (45,3 %) representatives of non-indigenous ethnic group. The second stage of the study involved 525 patients with HTN (317 shors, 208 non-indigenous representatives). According to the recommendations of National Guidelines of the Russian Society of Cardiology/the Russian Medical Society on Arterial Hypertension (2010), antihypertensive therapy was prescribed by a cardiologist. A re-examination of patients with HTN included in the prospective stage of the study was carried out after a month, 3 months and 6 months by a paramedic of the local feldsher-obstetric center and after 12 months by a cardiologist. Gene polymorphism ACE (I/D, rs 4340), AGT (c. 803T > C, rs699), AGTR 1 (А1166С, rs5186), ADRB 1 (с. 145A > G, Ser49Gly, rs1801252), ADRA2B (I/D, rs28365031), MTHFR (c. 677C > T, Ala222Val, rs1801133) and NOS 3 (VNTR, 4b/4a) were tested using polymerase chain reaction. Results. In the Shors cohort, the minor allele D of the ACE gene and the favorable allele A of the AGTR 1 gene were associated with a significant decrease in blood pressure (BP) with the 2-component therapy for HTN using blockers of the renin-angiotensin-aldosterone system (RAAS) with a diuretic (odds ratio (OR) = 5,01 and OR = 6,28). The carriage of the mutant allele D of the ACE gene in subjects with the 3-component therapy (RAAS blocker, calcium channel blocker (CCB), diuretic) also determined the achievement of the target BP level (OR = 3,11). In the cohort of non-indigenous nationality, allele A of the AGTR 1 gene was associated with positive dynamics of BP with the use of another combination therapy with a RAAS blocker and CCB (OR = 5,38). Conclusions. Taking into account the ethnicity, genetic characteristics of the patient when choosing drugs is a key point in the effectiveness of therapy in HTN patients. The possibility of using pharmacogenetics in the practice of a cardiologist opens up promising areas and has a great future.