A familial risk of chronic renal failure among blacks on dialysis?

Ferguson, R. L.; Grim, Clarence E.; Opgenorth, Terry J.

doi:10.1016/0895-4356(88)90023-6

Cited by 97 publications

(69 citation statements)

References 9 publications

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“…12 In addition, a genetic contribution to the increased prevalence of renal disease among hypertensive blacks has been proposed on the basis of family studies and studies of associated histocompatibility antigens. [13][14][15] To further narrow genetic heterogeneity, we have chosen to study a subset of blacks with both hypertension and elevated serum cholesterol levels. Family studies suggest that the phenotype of hypertension in combination with elevated cholesterol is heritable and is associated with accelerated cardiovascular disease.…”

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confidence: 99%

Genetic Determinants of Hypertension

Kotchen

Grim

et al. 2000

Hypertension

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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, ...

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confidence: 99%

Genetic Determinants of Hypertension

Kotchen

Grim

et al. 2000

Hypertension

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“…[23][24][25][26][27] Essential hypertension is a common syndrome, likely polygenic, which occurs with far higher prevalence in blacks compared with the general U.S. population. 28 ESRD is also especially common in blacks, 29 -31 and hypertension is a particularly prominent antecedent of the nephrosclerosis diagnosis, 26,[32][33][34] which seems to aggregate in black families. 32,34,35 Recent studies of the epidemiology of black ESRD, and the search for sources of genetic risk, coincide with studies of genetic (essential) hypertension.…”

Section: Heredity and Esrdmentioning

confidence: 99%

“…28 ESRD is also especially common in blacks, 29 -31 and hypertension is a particularly prominent antecedent of the nephrosclerosis diagnosis, 26,[32][33][34] which seems to aggregate in black families. 32,34,35 Recent studies of the epidemiology of black ESRD, and the search for sources of genetic risk, coincide with studies of genetic (essential) hypertension. 36 -39 In light of these observations, there is growing interest in the search for sources of genetic risk of ESRD in blacks.…”

Section: Heredity and Esrdmentioning

confidence: 99%

“…41 There is emerging interest in the role of susceptibility genes in complex human disease traits, such as ESRD, which displays familial aggregation yet whose genetic underpinnings are still obscure. 32,34 Genetic variants so far associated with nondiabetic ESRD include polymorphisms at renal kallikrein (KLK1), 38 Wilms' tumor proto-oncogene (WT1), 42 podocin (NPHS2), 43 IL-1A, 44 and TRPC6. 45 Because blacks may display exaggerated autonomic responses to environmental stressors 46 -49 and the sympathetic nervous system plays a role in creating or accelerating renal injury and thereby determining the rate of progression of renal disease, 50 -52 we explored whether polymorphisms at loci encoding components of the sympathetic neuroeffector junction 53 influenced risk of ESRD in a population enriched for hypertensive ESRD: blacks.…”

Section: Heredity and Esrdmentioning

confidence: 99%

“…Familial aggregation of ESRD from a number of causes has repeatedly been observed. 32,34,40 Although some cases of ESRD result from single gene mutations (approximately 8% of cases), most of the available evi- Wild-type (C ϩ87) versus common variant (ϩ87T) CHGA 3Ј-UTRs was inserted just 3Ј of the firefly luciferase reporter cassette in the luciferase reporter plasmid pGL3-Promoter (Promega) under the control of the SV40 early promoter. Forty-eight hours after transfection, cells were harvested for measurement of luciferase reporter activity, with results normalized (for transfection efficiency) to the activity of Renilla luciferase, from the cotransfected pRL-TK (Promega).…”

Section: Heredity and Esrdmentioning

confidence: 99%

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Chromogranin A Polymorphisms Are Associated With Hypertensive Renal Disease

Salem

Cadman²,

Chen³

et al. 2008

Journal of the American Society of Nephrology

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Chromogranin A is released together with epinephrine and norepinephrine from catecholaminergic cells. Specific endopeptidases cleave chromogranin A into biologically active peptide fragments, including catestatin, which inhibits catecholamine release. Previous studies have suggested that a deficit in this sympathetic "braking" system might be an early event in the pathogenesis of human hypertension. Whether chromogranin A (CHGA) polymorphisms predict end-organ complications of hypertension, such as end-stage renal disease, is unknown. Among blacks, we studied common genetic variants spanning the CHGA locus in 2 independent case-control studies of hypertensive ESRD. Two haplotypes were significantly more frequent among subjects with hypertensive ESRD: 1) in the promoter (5Ј) region, G-462A3T-415C3C-89A, haplotype ATC (adjusted odds ratio ϭ 2.65; P ϭ 0.037), and 2) at the 3Ј-end, C11825T (3Ј-UTR, Cϩ87T)3G12602C, haplotype TC (adjusted odds ratio ϭ 2.73, P ϭ 0.0196). Circulating levels of catestatin were lower among those with hypertensive ESRD than controls, an unexpected finding given that peptide levels are usually elevated in ESRD because of reduced renal elimination. We found that the 3Ј-UTR ϩ 87T variant decreased reporter gene expression, providing a possible mechanistic explanation for diminished catestatin. In summary, common variants in chromogranin A associate with the risk of hypertensive ESRD in blacks.

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