The role of gene polymorphisms (angiotensinconverting enzyme, tumor necrosis factor-alpha, and endothelial nitric oxide synthase) in the pathogenesis and treatment of chronic heart failure: Can gene polymorphism testing predict the effectiveness of p

Genetic markers commonly used in research into the multigenic basis of chronic heart failure (CHF) include polymorphic gene variants whose protein products are involved in the pathogenesis of this clinical syndrome.Polymorphisms in genes such as angiotensin-converting enzyme (ACE), tumor necrosis factor-alpha (TNF-), and endothelial nitric oxide synthase (eNOS) appear particularly significant, given their influence on arterial blood pressure regulation, endothelial function, and inflammatory processes-all critical factors in CHF progression.It has been demonstrated that the ACE deletion/deletion (DD) genotype, associated with increased angiotensin II-converting enzyme activity in the blood, may predispose individuals to CHF, reduce left ventricular ejection fraction (LVEF), and increase left ventricular end-systolic volume in post-myocardial infarction patients.Additionally, this genotype correlates with diminished exercise tolerance in patients with CHF.Similarly, the Key words chronic heart failure (CHF), gene polymorphism, angiotensin-converting enzyme (ACE), tumor necrosis factor-alpha (TNF-), endothelial nitric oxide synthase (eNOS).Physiotherapy Review | Volume XXIX Issue 2/2025 CC genotype of the TNF- polymorphism, compared to the CT and TT genotypes, is characterized by elevated blood TNF- levels, significantly reduced LVEF, and a fourfold increased risk of mortality in CHF patients.Furthermore, the Gl-u298Asp allele of the eNOS gene has been observed to reduce mortality risk in patients with severe dilated cardiomyopathy.Conversely, the presence of the CC genotype of the eNOS gene polymorphism (rs2070744) significantly increases mortality compared to the TT genotype in patients with CHF.Researchers indicate that the CC genotype serves as an independent prognostic marker of mortality risk in CHF patients, irrespective of age, LVEF values, and maximal oxygen consumption (VOmax) levels.