Genetic Determinants of Hypertension

Abstract

Abstract-Our long-term objective is to identify genes whose expression results in hypertension and in phenotypic changes that may contribute to hypertension. The purpose of the present study was to describe evidence for the heritability of hypertension-related phenotypes in hypertensive, hyperlipidemic black sib pairs. Outpatient anthropomorphic measurements were obtained in Ͼ200 affected sib pairs. In addition, 68 of these sib pairs were studied under controlled, standardized conditions at an inpatient clinical research center while off both antihypertensive and lipid-lowering medications. Heritability was estimated on the basis of sib-sib correlations and with an association model. Higher heritability estimates for blood pressure were observed with 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, and norepinephrine infusion; (2) plasma renin, aldosterone, epinephrine, and cAMP and cGMP responses to the assumption of upright posture; (3) para-aminohippurate and inulin clearances in response to norepinephrine infusion; and (4) plasma arginine vasopressin in response to NaCl infusion. High heritability estimates were also observed for various measures of body size and body fat, left ventricular size, cardiac index, stroke volume, total peripheral resistance, and serum concentrations of LDL and HDL cholesterol and leptin. These heritability estimates identify the hypertension-related phenotypes that may facilitate the identification of specific genetic determinants of hypertension in blacks with hyperlipidemia. (Hypertension. 2000;36:7-13.)Key Words: blacks Ⅲ cholesterol Ⅲ genetics Ⅲ phenotype A doption, twin, and family studies document a significant heritable component to blood pressure levels and hypertension. [1][2][3] Estimates of the heritability of resting systolic and diastolic blood pressures, based on family studies, are generally in the range of 15% to 35%. In twin studies, heritability estimates of blood pressure are Ϸ60% for males and Ϸ30% to 40% for females. 2 A heritable component to salt sensitivity of blood pressure has been described in blacks. 4 A large proportion of the phenotypic variation in blood pressure appears to be inherited as a polygenic trait. 5,6 Our long-term objective is to identify genetic loci and specific genes whose expression results in hypertension and in phenotypic changes that may contribute to hypertension.Blacks are one focus of our studies. In the United States, the prevalence of hypertension is 50% greater in blacks than in whites. 7 In blacks, hypertension appears earlier, is generally more severe, and results in high rates of morbidity and mortality from stroke, heart failure, ...

Heritability of Ambulatory and Beat-to-Beat Office Blood Pressure in Large Multigenerational Arab Pedigrees: The ‘Oman Family Study’

“…Although these studies were conducted in ethnically different populations, Fava et al (2004) reported somewhat lower heritability estimates for 24-hour and daytime ambulatory BP, whereas heritabilities for the sleep period were somewhat higher than those found in our study; heritability estimates for the 24-hours in Tomaszewski et al (2010) were comparable with our study, while Bochud et al (2005) reported higher heritabilities during sleep than the OFS did. The findings of OFS and other previous studies confirm the findings of Kotchen et al (2000), who found higher heritability estimates for multiple BP measurements averaged over 24 hours compared with single BP measurements in black sibpairs. To estimate heritabilities for multiple traits, we recorded an average of 700 measurements in 10 minutes during absolute resting conditions.…”

“…A potential limitation of this study compared with the one by Kotchen et al (2000) was that we did not measure ambulatory BP in the office where, aside from being in an environment setting different from a clinical one, both upper arms are used by the cuffs of the impedance unit (TFM). Our study aimed to reduce the number of procedures taken during the short time period when subjects were in the office.…”

“…Studies on twins, large cohorts, and isolated pedigrees have provided more insight into understanding complex traits of hypertension compared with case-control association studies (Hiekkalinna et al, 2012;Wang et al, 2011;Wu et al, 2010). In addition, genetic studies using ambulatory blood pressure (BP) measurements as a phenotype were found to be potentially more powerful than those using office BP measured in the clinic (Fava et al, 2004;Kotchen et al, 2000;Kupper et al, 2005;Tomaszewski et al, 2010;Wang et al, 2009). A distinct advantage is that ambulatory recordings allow collection of multiple day and night values in a natural setting.…”

Genetic Influence on Left Ventricular Structure and Function: A Korean Twin and Family Study

“…The combined twin and family design of our study could overcome the limitations of twin-only or family-only studies and provides a more accurate estimation of heritability by comparing the phenotypic correlations between diverse family relationships of different genetic correlations (Libhaber et al, 2009). Among ethnic groups, the heritability of LV mass tends to be higher for African-Americans (0.34-0.72;Fox et al, 2010;Harshfield et al, 1990;Kotchen et al, 2000) and those of Caribbean Hispanic descent (0.49; Juo et al, 2005) than for Americans, Europeans (0.076-0.32; Devereux et al, 1997;Garner et al, 2000;Mayosi et al, 2002;Palatini et al, 2001;Post et al, 1997), or American Indians (0.17;Bella et al, 2004). There have been two studies of heritability of LV structure for Asian populations (Assimes et al, 2007;Chien et al, 2006).…”

Genetic influence on blood pressure measured in the office, under laboratory stress and during real life

“…Because ABP is a better predictor of target organ damage, cardiovascular morbidity and mortality than office BP, 6–8 it is of great interest to know whether 24-h BP will be a better phenotype than office BP to find genes for EH. To date, four twin studies 25–28 and three family studies 29–31 have reported heritability estimates for 24-h ABP recording. However, only three studies 25,30,31 reported the heritability estimates both for office and 24-h BP, with two family studies 30,31 observing higher heritability and one twin study observing similar heritability for 24-h BP.…”