New Genetically Determined Markers of the Functional State of the Cardiovascular System

Abstract

Nowadays, cardiovascular diseases (CVDs) occupy a leading position in population mortality. Since it is known that the development of cardiovascular pathologies is determined mainly by the human genetic burden, an urgent task of primary prevention of CVDs is to assess the contribution of gene polymorphism to the formation of cardiovascular risk. The material for the study was the blood of volunteers aged 21 to 102 years. Polymorphisms were determined by real-time PCR. Multichannel volumetric sphygmography was performed to analyze the functional state of the vascular wall. The study revealed that the rs5742904 polymorphism of the ApoB gene was found to be absent in the studied groups of long-livers and descendants of long-livers. Results indicated that the carriage of the heterozygous variant of the MMP9 polymorphism is associated with a favorable prognosis for cardiovascular system functioning. A tendency towards an increase in the rate of biological age acceleration among subgroups with AA and GG genotypes of the MMP9 gene and a negative value of biological age acceleration among heterozygous carriers of this polymorphism allele were found. The conducted studies make it possible to identify new associations of the studied polymorphisms with the functional state of the cardiovascular system, which is of great clinical importance and requires further study.

Keywords: apolipoprotein B; cardiovascular disease; matrix metalloproteinases; methylenetetrahydrofolate reductase; single nucleotide polymorphism; sphygmography; type 1 collagen; vascular wall.

Figure 1

Indicators of systolic (a) and diastolic (b) blood pressure (BP) in the study group of individuals, depending on the genotypes of polymorphism rs17576 of the MMP9 gene; *—differences were considered significant at a corrected p-value (p) < 0.05 (Kruskal–Wallis test, post-hoc Dunn’s test 2-stage FDR correction).

Figure 2

Body mass index values in the study group of individuals depending on the genotypes of polymorphism rs17576 of the MMP9 gene; *—differences were considered significant at a corrected p-value (p) < 0.05 (Kruskal–Wallis test, post-hoc Dunn’s test 2-stage FDR correction).

Figure 3

The presence of hypertension in the study group of individuals depending on the genotypes of the polymorphism rs17576 of the MMP9 gene; *—differences were considered significant at a corrected p-value (p) < 0.05 (χ² test, post-hoc pairwise χ² test Benjamini–Hochberg FDR correction).

Figure 4

The acceleration value of biological age calculated by the PhenoAge model in the study group of individuals depending on the genotypes of the polymorphism rs17576 of the MMP9 gene. No significant differences at a corrected p-value (p) < 0.05 (Kruskal–Wallis test).

Figure 5

The distribution of study participants by clusters depending on the combination of genotypes in the population of residents of the Nizhny Novgorod region. A cluster was defined as a group of at least 10 participants.

Figure 6

Differences in systolic (a) and diastolic (b) blood pressure (BP) among the obtained clusters; *—differences were considered significant at a corrected p-value (p) < 0.05 (Kruskal–Wallis test, post-hoc Dunn’s test 2-stage FDR correction).

Figure 7

The presence of hypertension among the studied groups, depending on clusters; *—differences were considered significant at a corrected p-value (p) < 0.05 (χ² test, post-hoc pairwise χ² test Benjamini–Hochberg FDR correction).