Effect of ACE Gene D Allele (rs1799752) on Efficacy of Angiotensin-Converting Enzyme Inhibitors: A Pilot Study

INTRODUCTION. Arterial hypertension remains one of the leading causes of cardiovascular morbidity and mortality, however, data on the effect of genetic polymorphisms on the efficacy and safety of angiotensin-converting enzyme (ACE) inhibitors are contradictory and fragmentary. The effectiveness of antihypertensive therapy may also decrease with smoking, overweight, excessive salt intake, and type 2 diabetes mellitus (T2DM). A comprehensive assessment of the effect of ACE gene polymorphisms and confounders will allow correct interpretation of the causes of variability in the effectiveness of ACE inhibitors and optimization of therapy.

AIM. This study aimed to evaluate the effect of the ACE gene D allele (I/D rs1799752) and concomitant confounders (age, sex, smoking, overweight, excess salt intake, type 2 diabetes mellitus) on the efficacy of ACE inhibitors in patients with arterial hypertension in a pilot study, and to determine the feasibility of genotyping for predicting achievement of target blood pressure.

MATERIALS AND METHODS. A pilot pharmacogenetic study was conducted with the participation of 90 ambulatory patients of both sexes with newly diagnosed arterial hypertension in the period from February to May 2025. Genotyping results of blood samples was tested for Hardy–Weinberg equilibrium with a correction for small groups. Quantitative data were tested for normality. The correlation was assessed using Fisher’s exact test (95% CI) with Cramér’s V for strength of association. An AUC-ROC prognostic model was built to assess the sensitivity and specificity of the effect of genotype on achieving target blood pressure (BP) <140/90 mmHg.

RESULTS. After receiving ACE inhibitor therapy, 39 patients achieved target blood pressure values (II — 34 (87.2%); ID — 5 (12.8%); DD — 0 (0%)), while 51 patients did not (II — 1 (0.7%); ID — 33 (67.4%); DD — 17 (33.3%)). The poly­morphic ACE gene D allele (rs1799752) was significantly associated with failure to achieve target BP on ACE inhibitor therapy (Fisher’s exact test, p<0.001; Cramér’s V=0.82). ROC analysis of the number of D alleles showed high discriminatory ability for predicting target BP failure (AUC=0.947; 95% CI: 0.899–0.996). Among confounders, excess salt intake was significantly associated with target BP failure (p<0.05), whereas sex, age, type 2 diabetes mellitus, smoking, and overweight showed no significant association (p>0.05).

CONCLUSIONS. Carriage of the ACE gene D allele (rs1799752) and excess salt intake were associated with an increased risk of failing to achieve target BP on ACE inhibitor therapy, while other confounders demonstrated no clinically significant predictive role. Because of the small sample size and homogeneity, these findings should be considered preliminary and require confirmation in larger multicenter studies.

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