[Association of AGT, ACE, NOS3, TNF, MMP9, CYBA polymorphism with subclinical arterial wall changes]

Kardiologiia. 2021 Mar 30;61(3):57-65. doi: 10.18087/cardio.2021.3.n1212.
[Article in Russian]

Abstract

Aim Activation of the renin-angiotensin-aldosterone system, decreased nitric oxide production, chronic inflammation, and oxidative stress result in subclinical changes in the arterial wall, which favor the development of cardiovascular diseases (CVD). The effect of allelic gene variants that encode the proteins participating in pathogenetic pathways of age-associated diseases with subclinical changes in the arterial wall [increased pulse wave velocity (PWV), increased intima-media thickness, endothelial dysfunction (ED), presence of atherosclerotic plaques (ASP)] are understudied. This study analyzed the relationship between AGT, ACE, NOS3 TNF, MMP9, and CYBA gene polymorphism and the presence of subclinical changes in the arterial wall, including the dependence on risk factors for CVD, in arbitrarily healthy people of various age.Material and methods The relationship of polymorphisms с.521С>Т of AGT gene, Ins>Del of AСE gene, с.894G>T of NOS3 gene, - 238G>A of TNF gene, - 1562С>T of MMP9 gene, and c.214Т>С of CYBA gene with indexes of changes in the arterial wall and risk factors for CVD was studied in 160 arbitrarily healthy people by building models of multiple logistic regression and also by analyzing frequencies of co-emergence of two signs with the Pearson chi-squared test (χ2) and Fisher exact test.Results The DD-genotype of Ins>Del ACE gene polymorphism was correlated with increased PWV (p=0.006; odds ratio (OR) =3.41, 95 % confidence interval (CI): 1.48-8.67) and ED (p=0.014; OR=2.60, 95 % CI: 1.22-5.68). The GG genotype of с.894G>T NOS3 gene polymorphism was correlated with ED (p=0.0087; OR=2.65, 95 % CI: 1.26-5.72); the ТТ-genotype of с.894G>T NOS3 gene polymorphism was correlated with ASP (p=0.033; OR=0.034, 95 % CI: 0.001-0.549).Conclusion Polymorphic variants of AСE and NOS3 genes correlated with ED, increased arterial wall stiffness, and the presence of subclinical changes in the arterial wall.

MeSH terms

  • Alleles
  • Carotid Intima-Media Thickness
  • Humans
  • Matrix Metalloproteinase 9*
  • NADPH Oxidases
  • Nitric Oxide Synthase Type III / genetics
  • Polymorphism, Genetic
  • Pulse Wave Analysis*

Substances

  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • NADPH Oxidases
  • CYBA protein, human
  • MMP9 protein, human
  • Matrix Metalloproteinase 9