Genetic determinants of hypertension - Identification of candidate phenotypes

Our long-term objective is to identify genes whose expression results in hy pertension and in phenotypic changes that may contribute to hypertension. T he purpose of the present study was to describe evidence for the heritabili ty of hypertension-related phenotypes in hypertensive, hyperlipidemic black sib pairs. Outpatient anthropomorphic measurements were obtained in >200 a ffected sib pairs. In addition, 68 of these sib pairs were studied under co ntrolled, standardized conditions at an inpatient clinical research center while off both antihypertensive and lipid-lowering medications. Heritabilit y was estimated on the basis of sib-sib correlations and with an associatio n model. Higher heritability estimates for blood pressure were observed wit h multiple measurements averaged over 24 hours than with measurements at a single time point, and heritability estimates for nighttime blood pressures were higher than those for daytime blood pressures. Heritability estimates for several of the phenotypes were augmented by obtaining measurements in response to a standardized stimulus, including (1) blood pressure responses to the assumption of upright posture, standardized psychological stress, a nd norepinephrine infusion; (2) plasma renin, aldosterone, epinephrine, and cAMP and cGMP responses to the assumption of upright posture; (3) para-ami nohippurate and inulin clearances in response to norepinephrine infusion; a nd (4) plasma arginine vasopressin in response to NaCl infusion. High herit ability estimates were also observed for various measures of body size and body fat, left ventricular size, cardiac index, stroke volume, total periph eral resistance, and serum concentrations of LDL and HDL cholesterol and le ptin. These heritability estimates identify the hypertension-related phenot ypes that may facilitate the identification of specific genetic determinant s of hypertension in blacks with hyperlipidemia.