The question of mechanisms of mediated changes based on molecular genetic predispositions modified and unmodified risk factors still need further research.
For the first time, it was found that the missense mutation of the AGT gene (704T>C / rs699) in the homozygous state among residents of Northern Bukovina with EAH occurs in 56% of people, which is 12.5% more often than the TT-genotype (2=4,50; p=0.034), in contrast to the control group, where the specified difference is not statistically significant. The presence of polymorphic variants of the AGT (rs699) and VDR (rs2228570) genes are not predictors of the appearance of hypertension in the examined population. However, a more severe course of EAH is probably more common in the T-allele carriers, especially the TT-genotype of the AGT gene (rs699) - by 48.95% and 23.14%, respectively (p=0.006). Genotypes of the VDR gene (FokI/rs2228570) are not associated with a severity of EAH according to blood pressure levels.
Refined data on associations of modified and unmodified risk factors and polymorphism of the above genes in the examined population were also obtained. The presence of the T-allele of the AGT gene (rs699) (TT- and especially TС-genotypes) and the A-allele of the VDR gene (rs2228570) (AA- and especially AG-genotypes) in the genome of a patient with EAH increases the risk of obesity in almost 6 and 11.5 times [OR=5.92; p<0.001] and almost 4 and 8 times [OR=3.95; p=0.05 and OR=7.71; p=0.001], respectively, with a probably lower probability of these individuals having a normal body weight (p<0.001). The course of EAH in carriers of the T-allele (especially TC-genotype) of the AGT gene (rs699) and the A-allele of the VDR gene (rs2228570) is characterized by a more frequent burden of heredity for cardiovascular pathology by 28.63% (2=7.0; p=0.008), 35% (2=5.10; p=0.024) and 26.7% (2=5.21; p=0.022), respectively.
The theory of changes in metabolic parameters during EAH, taking into account polymorphic variants of the studied genes, gained further development:the presence of the T-allele of the AGT gene (rs699) in a patient with EAH increases the risk of hypertriglyceridemia by almost three times [OR=2.91; p=0.045], the probability of high atherogenicity index is more than 3.5 times higher [OR=3.57; p=0.02] and an increased waist-hip ratio in women - almost tripled [OR=2.83; p=0.05]. The presence in the genotype of the A-allele of the VDR gene (rs2228570) increases the risk of general hypercholesterolemia and the growth of atherogenicity index by almost 2.5 times [OR=2.46; p=0.044 and OR=2.44; p=0.043] for the lowest chances of the above-mentioned disorders in carriers of the GG genotype (p<0.05). The AA-genotype carriers of the VDR gene also have a more than 2-fold increase in the probability of elevated low density lipoprotein cholesterol [OR=2.37; p=0.04]. The risk of hypovitaminosis 25(OH) D increases in EAH patients with the T-allele of the AGT gene (rs699) in the genotype almost 7 times [OR=6.80; p=0.038], due to the protective role of the CC-genotype. And the risk of hypocalcemia increases more than 6 times in hypertensive patients with the GG-genotype of the VDR gene (rs2228570) [OR=6.25; p=0.046], with the lowest chances for carriers of the A-allele.
For the first time, it was clarified that 2-3 degrees of obesity (BMI ≥35 kg/m2) is associated with a higher relative number of patients with a low blood vitamin D level (<30 ng/ml) - by 38.71-55.56% (p=0.0015). In addition, the risk of fatal cardiovascular events on the SCORE scale >5.0 increases by almost 4.5 times in patients with EAH [OR=4.47; p<0.001]. The risk of stroke increases in patients with EAH with a decrease in the concentration of vitamin D almost three times [OR=3.01; p=0.009], as well as in the presence of the T-allele of the AGT gene (rs699) and the A-allele of the VDR gene (rs2228570) in the genome of a patient with EAH - in 11.5 [OR=5.92; p<0.001] and 8 times [OR=7.71; p=0.001], respectively.
The relationship between VDR (rs2228570) and AGT (rs699) genes was established with anthropometric and metabolic-hormonal parameters: the correlation matrix proved the inverse relationship of blood vitamin 25(OH) D with BMI, OT and OS (in C carriers -allele of the AGT gene (rs699) and GG-genotype of the VDR gene (rs2228570) r=-0.37-/-0.59/ (р≤0.05-0.006)). In patients with EAH, ionized Ca2+ is marginally negatively correlated with glucose level in individuals with the GG-genotype of the VDR gene r=-0.43 (р=0.052) and BMI and SBP in patients with the T-allele of the AGT gene r=-0.39 -/-0.71/ (р≤0.02-0.01), positive with PTH in carriers of the CC genotype of the AGT gene r=0.70 (р=0.001). PTH in patients with EAH positively correlates with anthropometric indicators of OT/OS, or OT, OS (in carriers of the T-allele of the AGT gene r=0.31-0.63 (р≤0.05-0.024) and, GG- genotype of the VDR gene r=0.50-0.56 (р≤0.025-0.01).
