Effectiveness of personalized selection of antihypertensive therapy based on genetic polymorphism

Abstract

Recent data indicate that it is important to develop the problem of genetic polymorphism in patients with arterial hypertension (AH) for the long-term possibility of using it as a justification for choosing the optimal treatment strategy. Currently, despite the availability of effective antihypertensive agents, the percentage of patients who have reached the target blood pressure level remains still not enough. A rational basis for choosing a particular class of drugs and / or their combinations in a concrete patient with AH can be the detection of genetic markers that determine the degree of sensitivity to therapy, since the relationship of its effectiveness with the genetic features is not in doubt today. Material and methods The work is based on the results of a clinical, instrumental, laboratory and genetic examination of 41 patients with AH with insufficient effectiveness of previous antihypertensive therapy. The median age and duration of the disease were 54 (32; 70) years and 7 (1; 20) years, respectively. Taking into account the identified gene polymorphism, a fixed combination of an ACE inhibitor (perindopril 10 mg) and a thiazide-like diuretic (indapamide 2.5 mg) was assigned. The comparative dynamics of blood pressure daily monitoring, left ventricle echocardiographic parameters, as well as indicators of vascular wall stiffness were analyzed before therapy and 3 months later. Results The study established a relationship between the clinical and morpho-functional features of AH in the examined patients with polymorphism of the AGT, AGTR2, CYP11B2, GNB3, NOS3 genes:-786 of their heterozygotes and “mutant” homozygotes, of which 3 polymorphic genes (AGT, AGTR2, CYP11B2) encode the activity of ACE. The obtained results allowed to establish that positive dynamics of the studied indicators was revealed in all patients. Though patients, carriers of the mutant allele C of polymorphic marker T704C AGT gene, had statistically significant more expressed benefit changes in blood pressure daily profile, echocardiographic parameters (such as left ventricular mass index, indicators of left ventricular diastolic function) and all parameters of arterial wall stiffness compared with patients who do not carry the “mutant” allele. Conclusion Thus, the selected treatment regimen demonstrated maximum antihypertensive, cardio - and vasoprotective effectiveness in the group of AH patients with the presence of the allele 704C of the polymorphic marker T704C of the AGT gene, which indicates the perspectivity of using genetic approaches to develop personalized tactics of AH patients drug treatment. Funding Acknowledgement Type of funding source: None