Ewa Barbara Kucio, Cezary Kucio

The influence of the I/D polymorphism of the angiotensin-converting enzyme gene on the pathogenesis and individualization of treatment of cardiovascular diseases

2026-06-19

Background. The subject of this study was the impact of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene on the pathogenesis and individualization of treatment for cardiovascular diseases.

Objectives. The aim of this paper was to present current knowledge regarding the role of the ACE gene I/D polymorphism in the pathogenesis of coronary artery disease, hypertension, and chronic heart failure, and to evaluate whether determining the ACE gene I/D polymorphism could contribute to the individualization of pharmacotherapy for these conditions.

Material and Methods. The PubMed database was searched for publications from its inception up to the year 2025. The searched keywords included: ACE gene I/D polymorphism or genetic variant ACE, coronary heart disease or coronary artery disease, hypertension, heart failure or chronić heart failure.

Results. Conducted studies have demonstrated that the DD genotype and the D allele itself of the ACE gene I/D polymorphism may be risk factors for CAD and myocardial infarction. However, there are reports where no such association was observed. Furthermore, no significant correlation was found between the ACE gene I/D polymorphism and the risk of in-stent restenosis or the pharmacological treatment used to prevent cardiovascular events (death, myocardial infarction). On the other hand, isolated studies have shown an impact of the II genotype on the effectiveness of cardiac rehabilitation in patients after myocardial infarction. Plasma and tissue ACE activity, along with the RAAS system, also play a major role in the pathogenesis of hypertension. Research has indicated an association between the DD genotype and the D allele and the incidence and course of hypertension. This association was dependent on the ethnic group of the subjects. The efficacy of pharmacological treatment was shown to be greater in hypertensive patients carrying the DD genotype of the ACE gene I/D polymorphism. However, large clinical trials (PROGRESS, GenHat) did not confirm these correlations. Coronary artery disease and hypertension are the most common causes of heart failure. Studies have shown that the DD genotype is a risk factor for developing heart failure in patients after myocardial infarction or with hypertension. There are also reports where no association between the ACE gene I/D polymorphism and heart failure was observed. Preliminary results of pharmacogenetic studies indicate that the ACE gene I/D polymorphism (DD genotype) may be a marker of response to pharmacological treatment (ACE inhibitors and beta-blockers) for heart failure, which varies by ethnicity.

Conclusions. The ambiguity of the study results regarding the impact of the ACE gene I/D polymorphism on the pathogenesis, course, and treatment of cardiovascular diseases probably stems from ethnic differences among the studied populations and the sample sizes of the study groups. For this reason, there is a clear need for further research.

Keywords: hypertension, heart failure, coronary artery disease, ACE gene I/D polymorphism.

© Farm Pol, 2025, 81(12): 691–702