THE SIGNIFICANCE OF THE NOS3 GENE C-786T POLYMORPHISM IN THE DEVELOPMENT OF ISCHEMIC HEART DISEASE

Ischemic heart disease is a multifactorial disease in which endothelial dysfunction and genetic predisposition play a significant role in its development. The aim of the study was to investigate the association of the C-786T polymorphism of the NOS3 gene, encoding endothelial nitric oxide synthase, with the risk of developing ischemic heart disease. The distribution of alleles and genotypes of this polymorphism was assessed in patients with ischemic heart disease and conditionally healthy individuals. Genotyping was performed using the polymerase chain reaction method with allele detection. The obtained results made it possible to assess the role of the C-786T polymorphism of the NOS3 gene in the formation of genetic predisposition to ischemic heart disease. The study of genetic factors involved in the regulation of endothelial function may contribute to improving early prediction of disease risk and the development of a personalized approach to the prevention of cardiovascular diseases.

Objective – to study the association of the C-786T polymorphism of the NOS3 gene, involved in the regulation of endothelial function and nitric oxide synthesis, with the risk of developing ischemic heart disease and to assess its potential role in the formation of genetic predisposition to the disease.

Materials and methods. The study included 210 patients with ischemic heart disease who were divided into two groups depending on the clinical variant of the disease. The first group consisted of 103 patients with unstable angina, including progressive angina, while the second group included 107 patients with stable exertional angina of functional class I–IV. The control group for genetic studies consisted of conditionally healthy individuals with no history of ischemic heart disease or other cardiovascular diseases and no family history of these diseases.

The study employed general clinical, biochemical, instrumental, molecular genetic, and statistical research methods. Genotyping of the C-786T polymorphism of the NOS3 gene was performed using the polymerase chain reaction method with allele detection. The frequencies of alleles and genotypes of the studied polymorphism were determined, and their distribution was comparatively analyzed between patients with ischemic heart disease and conditionally healthy individuals, as well as between patients with different clinical variants of the disease.

Results. Carriers of the heterozygous C/T genotype demonstrated a tendency toward a 1.5-fold increase in the risk of developing ischemic heart disease (χ² = 2.8; p = 0.17; OR = 1.5; 95% CI: 0.93–2.58).

Conclusion. The study revealed a statistically significant association between the C-786T polymorphism of the NOS3 gene and the risk of developing ischemic heart disease. The minor C allele was found to occur significantly more frequently in patients with ischemic heart disease and was associated with a 1.7-fold increase in disease risk. Carriage of the C/C and C/T genotypes was characterized by a tendency toward an increased risk of ischemic heart disease, with the most pronounced tendency observed among carriers of the C/C genotype.