Pharmacogenomic strategy for selection of hypotensive drugs and prospects for its use in pregnant women

Abstract

Cardiovascular disease (CVD) is one of the leading causes of death worldwide, and arterial hypertension (AH) is the strongest risk factor for its development. The problem of hypertension is also relevant during pregnancy, as high blood pressure can be dangerous for both the mother and the fetus, causing pre-eclampsia and premature birth. According to recent data, the number of patients with hypertension will increase. Because of the polygenic and multifactorial nature of the therapeutic response to drugs, further research in this area is needed to provide evidence- based guidelines for clinicians to optimize antihypertensive therapy. The purpose of this review was to summarize information from scientifi c publications, meta-analyses, guidelines for the years 2018-2023 regarding variants in genes that aff ect the metabolism of diff erent classes of drugs used in the treatment of hypertension, including during pregnancy, and related to the development of AH. The pathogenesis of hypertension is based on both a decrease in vasodilatation and an increase in circulating blood volume. Arterial stiff ness leads to a decrease in vasodilation, and water and sodium retention leads to an increase in blood volume. Additional factors such as the renin- angiotensin-aldosterone system, the sympathetic nervous system, and gene variants aff ect both vasodilation and blood volume. In addition, there are complex interactions among these factors. As an innate factor, gene variants can aff ect all of the above simultaneously. The American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines recommend the use of medications from the following 5 classes: diuretics, calcium channel blockers (CCBs), beta-adrenergic receptor blockers (beta- blockers), angiotensin- converting enzyme inhibitors, and angiotensin II receptor blockers. The studies included in this review used two main approaches: candidate gene analysis and genome-wide association analysis. The polygenic nature of hypertension greatly complicates the search for clinically relevant variants and relationships between individual genes and response to medications used to treat hypertension in diff erent ethnic groups. Candidate genes that may infl uence the risk of hypertension include voltage- dependent calcium channel genes (CACNA1A, CACNA1C, CACNA1S, and CACNB2), NEDD4L, ADD1, and miR. A number of genetic polymorphisms are associated with both the infl uence on the development of arterial hypertension and the response to treatment – eNOS, TRIB3, CYP, POR, ADRB1, ADRB2, ACE. When treating pregnant women with hypertension, the effi cacy of the antihypertensive agent must be balanced against the risk to the fetus. Initial antihypertensive therapy should include an acceptable fi rst-line agent. The development of a pharmacogenomic strategy to select the most eff ective and well tolerated drug treatment regimen for hypertension is of paramount importance, as it will lead to a lower number of drugs required per patient and better blood pressure control, help prevent cardiovascular and renal complications, and improve quality and length of life.