A primer on the genetics of hypertension

Cusi, Daniele; Bianchi, Giuseppe

doi:10.1046/j.1523-1755.1998.00007.x

Cited by 22 publications

(21 citation statements)

References 164 publications

(95 reference statements)

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“…In addition, the multivariate analysis shows no significant synergistic effect Essential hypertension has a well-known familial aggregation and has been calculated to be Ϸ40% genetically determined. 21 In the last decade, the development of PCR methodology has made possible the study of several genetic determinants of essential hypertension. The RAS has a central role in the regulation of BP and sodium homeostasis, 4 and genes that are involved in the activity of this enzyme cascade are potential candidate genes for essential hypertension or some associated clinical features.…”

Section: Discussionmentioning

confidence: 99%

Renin-Angiotensin System Genetic Polymorphisms and Salt Sensitivity in Essential Hypertension

et al. 2000

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Abstract-We evaluated the association between salt-sensitive hypertension and 3 different genetic polymorphisms of the renin-angiotensin system. Fifty patients with essential hypertension were classified as salt sensitive or salt resistant, depending on the presence or absence of a significant increase (PϽ0.05) in 24-hour ambulatory mean blood pressure (BP) after high salt intake. Key Words: angiotensin-converting enzyme Ⅲ genes Ⅲ angiotensin II Ⅲ blood pressure monitoring, ambulatory T he blood pressure (BP) response to increased dietary salt is heterogeneous among individuals, a phenomenon known as salt sensitivity. Normotensive and hypertensive salt-sensitive subjects tend to exhibit familial history of hypertension more frequently than salt-resistant subjects. 1,2 This suggests the existence of genetic determinants that influence BP sensitivity to sodium chloride. More than 10 years ago, Weinberger et al 3 reported a significant relation between haptoglobin 1-1 phenotype and BP response to intravenous sodium overload both in normotensive and hypertensive subjects.The renin-angiotensin system (RAS) has a central role in controlling BP and sodium homeostasis. 4 In the last decade, several authors have investigated RAS polymorphisms as genetic determinants of essential hypertension and end-organ damage. Although the results obtained are controversial, the presence of the D allele in intron 16 of the angiotensinconverting enzyme (ACE) gene appears to be associated with a higher risk for development of both macrovascular and microvascular disease in hypertensive individuals. 5 Moreover, the presence of the T allele in exon 2 of the angiotensinogen (AGT) gene appears to be associated with a higher risk for development of hypertension. 6 Finally, the association of the T allele of the AGT gene and the D allele of the ACE gene has a synergistic effect on the incidence of cerebrovascular disease, 7 and the association of the D allele of the ACE gene and the C allele of angiotensin II type 1 (AT1) receptor gene appears to increase the risk of myocardial infarction. 8 The RAS also is implicated in the BP response to salt intake. Low-renin hypertensives show an increased BP response to NaCl load, 9 and salt-sensitive individuals exhibit a blunted response of the RAS when they switch from low to high salt intake compared with salt-resistant subjects. 10 Moreover, plasma levels of ACE and angiotensinogen differ in subjects with different ACE and angiotensinogen genotypes. 11,12

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Section: Discussionmentioning

confidence: 99%

Renin-Angiotensin System Genetic Polymorphisms and Salt Sensitivity in Essential Hypertension

et al. 2000

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“…[1][2][3][4][5][6] It is thus of particular appeal in investigations aimed at identifying QTLs implicated in EHT and allied clinical manifestations. So far, however, both positive associations with EHT, family history of EHT and intermediate phenotypes [10][11][12][18][19][20][21][22][23] and negative results as for association or linkage studies with EHT [24][25][26][27][28][29][30][31][32][33][34][35][36] have been reported.…”

Section: Discussionmentioning

confidence: 99%

“…Those are complex disorders with multifactorial etiologies in which gene-gene and gene-environment interactions play a major role (for reviews, see references [1][2][3][4][5]. The considerable task facing molecular geneticists is to identify the quantitative trait loci (QTL) that are involved in the pathogenesis of essential hypertension (EHT) and stroke.…”

Section: Introductionmentioning

confidence: 99%

“…The considerable task facing molecular geneticists is to identify the quantitative trait loci (QTL) that are involved in the pathogenesis of essential hypertension (EHT) and stroke. [1][2][3][4][5][6] A number of candidate genes have been investigated by association, linkage and sib-pair linkage analyses. [6][7][8] These studies have led to mixed results as for putative involvements and roles of the concerned genes in the onset of the disorders.…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8] These studies have led to mixed results as for putative involvements and roles of the concerned genes in the onset of the disorders. [1][2][3][4][5][6][7][8][9] Using retrospective, association studies of the case-control type, we have previously shown that that renin (REN) gene variants (or variants of a neighbouring gene that lies in the vicinity of REN on chromosome 1) that are in linkage disequilibrium with two genetic markers, a dimorphic BglI site in intron 1 and a dimorphic MboI site in intron 9 of the REN gene, could be implicated in determining an individual's genetic susceptibility to EHT in two independent populations. [10][11][12] We looked here for putative associations between haplotypes constructed by combining these two markers and direct clinical diagnosis of EHT and stroke, and probed whether these associations occur through the effects of classical risk factors related to lipid disorders.…”

Section: Introductionmentioning

confidence: 99%

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Haplotypes of the human renin gene associated with essential hypertension and stroke

Lestringant

et al. 2000

J Hum Hypertens

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The human renin gene (REN) is a good candidate in studies aimed at unravelling the genetic basis of essential hypertension and stroke. We previously established that both a BglI and an MboI dimorphisms (located respectively in the first and ninth introns of the REN gene) were associated with essential hypertension in a population of hyperlipidaemic US subjects. In this association (retrospective case-control) study, we investigated the haplotype distribution of alleles defined by the combination of REN BglI and MboI dimorphic sites in 329 hyperlipidaemic US Caucasian subjects referred to UCSF Medical Center (140 hypertensives, 141 normotensives, and 48 hypertensive patients who had suffered a stroke). A statistically significant association

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Diuretic Therapy, the α-Adducin Gene Variant, and the Risk of Myocardial Infarction or Stroke in Persons With Treated Hypertension

Psaty¹,

Smith

Heckbert

et al. 2002

JAMA

187

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A primer on the genetics of hypertension

Cited by 22 publications

References 164 publications

Renin-Angiotensin System Genetic Polymorphisms and Salt Sensitivity in Essential Hypertension

Renin-Angiotensin System Genetic Polymorphisms and Salt Sensitivity in Essential Hypertension

Haplotypes of the human renin gene associated with essential hypertension and stroke

Diuretic Therapy, the α-Adducin Gene Variant, and the Risk of Myocardial Infarction or Stroke in Persons With Treated Hypertension

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