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RISK CONFERRED BY POLYMORPHIC VARIANTS OF VITAMIN D RECEPTOR (VDR) AND ANGIOTENSIN II TYPE 1 RECEPTOR (AGTR1) GENES FOR ESSENTIAL HYPERTENSION

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Objective: The aim of this study was to establish the role of 1166A>C polymorphism of the AGTR1 gene (rs5186) and A/G polymorphism of the VDR gene (rs2228570) in risk prediction of essential hypertension (EH). Design and method: The study included patients with EH and hypertensive-mediated organs damage (2nd stage), moderate, high/very high cardiovascular risk. 100 subjects were involved in the case-control study. There were 70.84% females, 29.16% males among them, the mean age was 57.86±7.81 yo. Age- and gender-matched controls (n = 60) whose blood pressure measurements were in normal range and without any apparent diseases were randomly selected to compare with the patient data. In order to detect AGTR1 (rs5186) and VDR (rs2228570) gene polymorphism the qualitative real-time polymerase chain reaction was done. AGTR1 gene genotyping was performed for 72 patients and 48 healthy individuals and VDR gene – for 100 patients and 60 healthy subjects. Results: The distribution of genotypes and alleles AGTR1 (rs5186) and VDR (rs2228570) in the study and control groups did not differ significantly (p>0.05). C-allele of AGTR1 gene (rs5186) increases the risk of EAH more than 2 times [OR–2.31; 95% CI OR:1.19–4.47; p = 0.011], as well as AC- and the combination of AC- + CC-genotypes [OR–2.09; 95% CI OR:1.03–4.25; p = 0.038 and OR–2.30; 95% CI OR:1.14–4.64; p = 0.017]. The epidemiological analysis showed that polymorphic variants VDR (rs2228570) genes are not the risk factors of EH in the observed. Although, the combination of wild alleles of both genes in the homozygous state (AAAGTR1/AAVDR) makes a protective effect [OR = 0,42; OR 95%CI:0,18-1,0; ⇙2 = 3,74; p = 0,05], the combination of minor alleles (C-allele AGTR1 /AAVDR+C-allele AGTR1/AGVDR) increases the risk of EH more than threefold [OR = 3,36; OR 95%CI:1,24-9,09; ⇙2 = 5,88; p = 0,015]. Conclusions: Genotypes and alleles of VDR (rs2228570) gene are not associated with the risk of developing EH in the examined. C-allele of AGTR1 gene (rs5186) increases the risk of hypertension more than 2 times [OR–2.31; p = 0.011]. Combination of minor C-allele of AGTR1 gene and A-allele of VDR gene (C-allele AGTR1 /AAVDR+C-allele AGTR1/AGVDR) escalates the risk of EH more than 3 times [OR = 3,36; p = 0,015].
Title: RISK CONFERRED BY POLYMORPHIC VARIANTS OF VITAMIN D RECEPTOR (VDR) AND ANGIOTENSIN II TYPE 1 RECEPTOR (AGTR1) GENES FOR ESSENTIAL HYPERTENSION
Description:
Objective: The aim of this study was to establish the role of 1166A>C polymorphism of the AGTR1 gene (rs5186) and A/G polymorphism of the VDR gene (rs2228570) in risk prediction of essential hypertension (EH).
Design and method: The study included patients with EH and hypertensive-mediated organs damage (2nd stage), moderate, high/very high cardiovascular risk.
100 subjects were involved in the case-control study.
There were 70.
84% females, 29.
16% males among them, the mean age was 57.
86±7.
81 yo.
Age- and gender-matched controls (n = 60) whose blood pressure measurements were in normal range and without any apparent diseases were randomly selected to compare with the patient data.
In order to detect AGTR1 (rs5186) and VDR (rs2228570) gene polymorphism the qualitative real-time polymerase chain reaction was done.
AGTR1 gene genotyping was performed for 72 patients and 48 healthy individuals and VDR gene – for 100 patients and 60 healthy subjects.
Results: The distribution of genotypes and alleles AGTR1 (rs5186) and VDR (rs2228570) in the study and control groups did not differ significantly (p>0.
05).
C-allele of AGTR1 gene (rs5186) increases the risk of EAH more than 2 times [OR–2.
31; 95% CI OR:1.
19–4.
47; p = 0.
011], as well as AC- and the combination of AC- + CC-genotypes [OR–2.
09; 95% CI OR:1.
03–4.
25; p = 0.
038 and OR–2.
30; 95% CI OR:1.
14–4.
64; p = 0.
017].
The epidemiological analysis showed that polymorphic variants VDR (rs2228570) genes are not the risk factors of EH in the observed.
Although, the combination of wild alleles of both genes in the homozygous state (AAAGTR1/AAVDR) makes a protective effect [OR = 0,42; OR 95%CI:0,18-1,0; ⇙2 = 3,74; p = 0,05], the combination of minor alleles (C-allele AGTR1 /AAVDR+C-allele AGTR1/AGVDR) increases the risk of EH more than threefold [OR = 3,36; OR 95%CI:1,24-9,09; ⇙2 = 5,88; p = 0,015].
Conclusions: Genotypes and alleles of VDR (rs2228570) gene are not associated with the risk of developing EH in the examined.
C-allele of AGTR1 gene (rs5186) increases the risk of hypertension more than 2 times [OR–2.
31; p = 0.
011].
Combination of minor C-allele of AGTR1 gene and A-allele of VDR gene (C-allele AGTR1 /AAVDR+C-allele AGTR1/AGVDR) escalates the risk of EH more than 3 times [OR = 3,36; p = 0,015].

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