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Blood pressure, arterial stiffness and endogenous lithium clearance in relation to AGTR1 A1166C and AGTR2 G1675A gene polymorphisms.

ABSTRACT: Although recently a matter of epidemiologic controversy, sodium overload and its interaction with genetic factors predispose to hypertension and related target organ complications.In 131 (66 male) treated hypertensives, we measured peripheral and central arterial pressures and pulse wave augmentation indexes (AIx(P), AIx(C1), AIx(C2)), pulse wave velocity (PWV), daily urinary sodium excretion and did genetic studies of AGTR1 A1166C and AGTR2 G1675A polymorphisms. Proximal (FE(Li)) and distal (FDR(Na)) sodium reabsorption measurements were performed using endogenous lithium clearance.In men, we found interaction between FDR(Na) and AGTR2 G1675A polymorphism with respect to AIx(C1) (p(INT)=0.01), AIx(C2) (p(INT)=0.05) and AIx(P) (p(INT)=0.006). Arterial stiffness increased with higher sodium reabsorption in the distal tubule, in the presence of AGTR2 G allele with the opposite tendency in A allele carriers. In the subgroup with FDR(Na) below median, as compared to those with FDR(Na) above median, the AIx(C1) (139.6±3.8 vs 159.1±5.7%; p=0.009), AIx(C2) (26.3±1.8 vs 33.3±1.7%; p=0.016) and AIx(P) (83.4±2.5 vs 96.5±2.6%; p<0.0001) were lower, in the G allele carrying men and GG homozygous women.The relation between sodium reabsorption in the distal tubule and the development of arterial stiffness depends on the AGTR2 G1675A polymorphism in blood pressure independent fashion.

SUBMITTER: Cwynar M

PROVIDER: S-EPMC5843941 | biostudies-literature | 2016 Apr-Jun

REPOSITORIES: biostudies-literature

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Blood pressure, arterial stiffness and endogenous lithium clearance in relation to AGTR1 A1166C and AGTR2 G1675A gene polymorphisms.

Cwynar Marcin M Gąsowski Jerzy J Głuszewska Anna A Królczyk Jarosław J Bartoń Henryk H Słowik Agnieszka A Grodzicki Tomasz T

Journal of the renin-angiotensin-aldosterone system : JRAAS 20160401 2

<h4>Introduction</h4>Although recently a matter of epidemiologic controversy, sodium overload and its interaction with genetic factors predispose to hypertension and related target organ complications.<h4>Methods</h4>In 131 (66 male) treated hypertensives, we measured peripheral and central arterial pressures and pulse wave augmentation indexes (AIx(P), AIx(C1), AIx(C2)), pulse wave velocity (PWV), daily urinary sodium excretion and did genetic studies of AGTR1 A1166C and AGTR2 G1675A polymorphi ...[more]

PMID: 27339867

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Project description:BackgroundThe differences in the antihypertensive treatment with angiotensin type II receptor blockers (ARBs) may be attributed to polymorphisms in genes involving drug-targeted receptor and drug metabolism. The present study aimed to investigate whether the antihypertensive effect of the ARB drug valsartan was associated with angiotensin II type 1 receptor (AGTR1) gene polymorphism (A1166 C) and cytochrome P450 enzyme 2C9 (CYP2C9) gene polymorphism (CYP2C9∗3).Methods281 patients with hypertension who received valsartan monotherapy in the past month were included in this retrospective study. Polymerase chain reaction-melting curve analysis was performed to genotype the AGTR1 and CYP2C9 gene polymorphisms. Based on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the time of visit, the patients were divided into well-controlled group (n = 144, SBP/DBP <140/90 mmHg) and poorly controlled group (n = 137, SBP/DBP ≥140/90 mmHg).ResultsOlder age, decreased history of drinking, a higher proportion of mild-to-moderate hypertension, lower alanine aminotransferase levels, and higher high-density lipoprotein cholesterol levels were observed in the well-controlled group than the poorly controlled group. Higher frequencies of the C allele and AC + CC genotype of AGTR1 A1166C were detected in the well-controlled than the poorly controlled patients (P = 0.005 and P = 0.006). After adjustment for demographic and environmental factors, the CC + AC genotype of AGTR1 A1166C was markedly linked to better hypertension control with valsartan treatment compared to the AA genotype (odds ratio: 2.836, 95% confidence interval: 1.199-6.705, P = 0.018). No significant difference was observed in the allele or genotype distribution of CYP2C9∗3 polymorphism between well-controlled and poorly controlled patients.ConclusionsThe current data suggested that the AGTR1 A1166 C polymorphism may be associated with the antihypertensive effect of valsartan, and carriers with AC and CC genotypes may have a better antihypertensive efficacy response to valsartan treatment.

Project description:ObjectiveArterial hemodynamics and vascular calcification are associated with increased risk for cardiovascular disease, but their inter-relations remain unclear. We sought to examine the associations of arterial stiffness, pressure pulsatility, and wave reflection with arterial calcification in individuals free of prevalent cardiovascular disease.Approach and resultsFramingham Heart Study Third Generation and Offspring Cohort participants free of cardiovascular disease underwent applanation tonometry to measure arterial stiffness, pressure pulsatility, and wave reflection, including carotid-femoral pulse wave velocity, central pulse pressure, forward wave amplitude, and augmentation index. Participants in each cohort (n=1905, 45±6 years and n=1015, 65±9 years, respectively) underwent multidetector computed tomography to assess the presence and quantity of thoracic aortic calcification, abdominal aortic calcification, and coronary artery calcification. In multivariable-adjusted models, both higher carotid-femoral pulse wave velocity and central pulse pressure were associated with greater thoracic aortic calcification and abdominal aortic calcification, whereas higher augmentation index was associated with abdominal aortic calcification. Among the tonometry measures, carotid-femoral pulse wave velocity was the strongest correlate of all calcification measures in multivariable-adjusted models (odds ratio per SD for thoracic aortic calcification, 2.69 [95% confidence interval, 2.17-3.35]; abdominal aortic calcification, 1.47 [95% confidence interval, 1.26-1.73]; and coronary artery calcification, 1.48 [95% confidence interval, 1.28-1.72]; all P<0.001, respectively). We observed stronger relations of carotid-femoral pulse wave velocity, central pulse pressure, and forward wave amplitude with nearly all continuous calcification measures in the younger Third Generation Cohort as compared with the Offspring Cohort.ConclusionsIn community-dwelling individuals without prevalent cardiovascular disease, abnormal central arterial hemodynamics were positively associated with vascular calcification and were observed at younger ages than previously recognized. The mechanisms of these associations may be bidirectional and deserve further study.

Dataset Information

Blood pressure, arterial stiffness and endogenous lithium clearance in relation to AGTR1 A1166C and AGTR2 G1675A gene polymorphisms.

Publications

Blood pressure, arterial stiffness and endogenous lithium clearance in relation to AGTR1 A1166C and AGTR2 G1675A gene polymorphisms.

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