title: Preferential association of aldosterone synthase gene polymorphism with central blood pressure and wave reflections in hypertensive individuals.
abstract: In hypertensive humans, the CC genotype of the aldosterone synthase gene polymorphism (ASGP) CYP11B(2) (C-344T variant) is associated with increased aortic stiffness. Whether ASGP is also associated with altered central (carotid) wave reflections has never been investigated. After 1-month wash-out period, 124 hypertensive individuals were submitted to measurements of brachial and carotid systolic blood pressure (SBP), aortic pulse wave velocity (PWV) and wave reflections, using the carotid augmentation index (CAI) determined from pulse wave analysis. Two age- and sex-adjusted models of the impact of ASGP were analysed. Comparing the ASGP-CC with ASGP-TT and -TC genotypes, the former had significantly stronger intergroup correlation coefficients for age or CAI vs heart rate relationships (P=0.008; P=0.02). Stepwise multiple regressions showed that carotid SBP was independently influenced by PWV and CAI, but only in individuals with the CC (P=0.0002; P=0.03) and TC genotypes (P=0.0004; P=0.004). Those associations were not, or only weakly, observed using the brachial artery SBP model. In conclusion, this study showed that, in hypertensive individuals, ASGP is not directly associated with the SBP level, but rather independently with its two main determinants, central PWV and wave reflections. The result was observed only for CC and TC genotypes. Such findings are observed when central, but not brachial, haemodynamic measurements are performed.
authors.affiliation: Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Blacher
authors.forename: A
authors.initials: A
authors.lastname: Kakou
authors.forename: J-M
authors.initials: JM
authors.lastname: Lacombe
authors.forename: M E
authors.initials: ME
authors.lastname: Safar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D001013:Aorta, Thoracic / Q000502:physiology; D001783:Blood Flow Velocity / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D001916:Brachial Artery / Q000502:physiology; D002339:Carotid Arteries / Q000502:physiology; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011673:Pulsatile Flow / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors; D055815:Young Adult
chemical_list: D019405:Cytochrome P-450 CYP11B2