Author:

Keywords:

Adult, Aldosterone Synthase, Alleles, Arteries, Blood Pressure, Cytosine, DNA Transposable Elements, Female, Gene Deletion, Heterozygote, Humans, Hypertension, Male, Middle Aged, Natriuresis, Peptidyl-Dipeptidase A, Polymorphism, Genetic, Thymine, Science & Technology, Life Sciences & Biomedicine, Peripheral Vascular Disease, Cardiovascular System & Cardiology, aldosterone synthase, anglotensin-converting enzyme, augmentation index, genetics, sodium, ALDOSTERONE SYNTHASE GENE, ANGIOTENSIN-CONVERTING-ENZYME, HAPLOTYPE ANALYSIS, BLOOD-PRESSURE, POLYMORPHISM, STIFFNESS, TRANSCRIPTION, HYPERTENSION, HEART, TRIAL, Cytochrome P-450 CYP11B2, European Project on Genes in Hypertension (EPOGH) Investigators, 1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences, 1116 Medical Physiology, Cardiovascular System & Hematology, 3201 Cardiovascular medicine and haematology, 3202 Clinical sciences

Abstract:

OBJECTIVE: Angiotensin II and aldosterone, generated by the angiotensin-converting enzyme (ACE) and aldosterone synthase (CYP11B2), respectively, not only regulate sodium and water homeostasis, but also influence vascular remodeling in response to high blood pressure. In the European Project on Genes in Hypertension (EPOGH), we therefore investigated whether the ACE I/D and CYP11B2 C-344T polymorphisms influence early arterial wave reflections, a measure of vascular stiffness. METHODS: We measured the peripheral and central augmentation index of systolic blood pressure by applanation tonometry at the level of the radial artery in 622 subjects (160 families and 64 unrelated individuals) randomly recruited from three European populations, whose average urinary sodium excretion ranged from 196 to 245 mmol/day. In multivariate analyses, with sodium excretion analyzed as a continuous variable, we explored the phenotype-genotype associations by means of generalized estimating equations and the quantitative transmission disequilibrium test. RESULTS: The peripheral and central augmentation indexes were significantly higher in CYP11B2 -344C allele carriers than in -344T homozygotes. In offspring, early wave reflections increased with the transmission of the -344C allele. This effect of the CYP11B2 polymorphism occurred in subjects with a higher than median urinary sodium excretion (210 mmol/day). The ACE I/D polymorphism did not influence augmentation of systolic blood pressure. CONCLUSIONS: The CYP11B2 C-344T polymorphism affects arterial stiffness. However, sodium intake seems to modulate this genetic effect.