Zuzana Malachovská, Miriam Kozárová, Martin Javorský, Ivan Tkáč
Introduction: Endothelial dysfunction (ED) is characterized as functional, reversible damage to endothelial cells resulting
from oxidative stress and changes in the bioavailability of nitric oxide. ED is an intermediate stage in the development
Aim: The aim of the study was to find out in the Slovak population the frequency of alleles and genotypes of selected gene
polymorphisms associated with the manifestations of subclinical atherosclerosis in peripheral arteries in the risky population
of type 2 diabetics.
Methods: Genetic association study included 124 asymptomatic type 2 diabetics of average age of 62,9 ± 9,1 years.
Each of the patients went through a complex vascular protocol aimed at detecting of subclinical atherosclerosis in the
peripheral arteries, specifically pulse wave velocity (PWV) measurement, intima-media thickness (IMT) and flow-mediated
dilation (FMD). The DAB2IP rs7025486, PAX2 rs6584389 and Hp rs72294371 gene polymorphisms were tested.
Results: The DAB2IP rs7025486, PAX2 rs6584389 and Hp rs72294371 polymorphisms were significantly associated with
intima-media thickness (IMT average and IMT of the left side). In multivariate linear regression analysis with mean IMT
as a dependent variable, among the genetic factors, the C allele of polymorphism PAX2 rs6584389 was a significant IMT
thickness predictor (β = 0,0460; p = 0,029). From the other genetic factors, the strongest predictors were: asymmetric
dimethylarginine (ADMA) (β=0,200; p = 0,022), glycated hemoglobin (HbA1c) (β = 0,0237; p = 0,003), male gender
(β = 0,0952, p = 0,011) and age (β = 0,00953; p < 0,001).
Conclusion: Due to the independence from traditional risk factors of atherosclerosis, detected gene polymorphisms,
DAB2IP rs7025486, PAX2 rs6584389 and Hp rs72294371, may point to new mechanisms of atherogenesis with potential
direct implication for practice in terms of individualization of therapy in carriers of these polymorphisms.