Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension

Zee, Robert Y.L.; Lou, Yi-kun; Griffiths, Lyn R.; Morris, Brian J.

doi:10.1016/0006-291x(92)91150-o

Cited by 249 publications

(107 citation statements)

References 18 publications

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“…0.12). The fact that the particular HT and NT populations examined in the present study are capable of yielding statistically significant results if a difference were to exist is supported by our recent findings of positive results for RFLPs of two unrelated genes (21,22).…”

Section: Discussionsupporting

confidence: 82%

“…After extraction of leukocyte DNA, 15 ,~g was cut with DraI or BgII, electrophoresed on 1 % agarose gels, and Southern blotting performed as described previously (18)(19)(20)(21)(22). Recombinant plasmids were labelled by nick-translation using [32PJ-dCTP (Amersham International, Amersham, Buckinghamshire, UK) to a specific activity of ---1 X 108 cpm/pg and used to probe DNA on Gene Screen Plus membranes.…”

Section: Rflp Analysesmentioning

confidence: 99%

“…Recombinant plasmids were labelled by nick-translation using [32PJ-dCTP (Amersham International, Amersham, Buckinghamshire, UK) to a specific activity of ---1 X 108 cpm/pg and used to probe DNA on Gene Screen Plus membranes. Hybridization was for 14-24 h at 42°C, followed by two high stringency washes in 15 mM NaCI, 1.5 mM sodium citrate, pH 7.0, at 65°C, and autoradigraphy as described previously (19)(20)(21)(22).…”

Section: Rflp Analysesmentioning

confidence: 99%

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Association Analyses of RFLPs for the .ALPHA.2- and .BETA.1-Adrenoceptor Genes in Essential Hypertension.

1992

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Adrenoceptor stimulation has an important role in normal cardiovascular regulation and a genetic defect could be a cause of essential hypertension (HT). The present study examined the relationship with HT of RFLPs for the a2-adrenoceptor gene (ADRA2R) and N 1-adrenoceptor gene (ADRBIR), which share the same chromosomal locus (10g24-26). Subjects were HTs and normotensives (NTs) whose parents had a similar blood pressure status at age ? 50. The frequency of the minor allele of the DraI RFLP of ADRA2R was 0.17 in HTs (n =76) and 0.17 in NTs (n = 87). For the BglI RFLP of ADRBIR, frequency of the minor allele was 0.10 in HTs (n = 62) and 0.12 in NTs (n = 88). x 2 analysis showed no difference between HT and NT groups. Thus the present study provides no basis for involvement of the a2-or N 1-adrenoceptor genes in essential hypertension. (Hypertens Res 1992; 15: 57-60) Key Words:molecular genetics, sympathetic nervous system, alleles, blood pressureThe sympathetic nervous system has been implicated in the onset of essential hypertension (HT), as well as in the adaptation of the heart to chronically elevated blood pressure (BP) (1). At least part of the increase in BP in HT could be a result of an alteration in adrenoceptor number, affinity or signal transduction, either as a response to variation in local catecholamine concentrations or other factors, or could be due to a primary genetic disturbance. The possibility that decreased central a2-adrenoceptor (a2AR) density or responsiveness may be involved in HT is suggested by the efficacy of a2AR agonists as anti-HT agents (1). /9-adrenoceptor (/9AR) responsiveness is reduced in HT (2, 3) and could contribute to the increased peripheral vascular resistance (4-7). Decreased sensitivity could be caused by a primary genetic defect or be a result of tonic down-regulation of /9ARs in response to elevated sympathetic activity (3, 8) or be due to disruption in signal transduction (9) as a consequence of reduced function of the stimulatory guanosine triphosphate-binding protein (10) or PAR kinase (I1). j91ARs mediate the positive inotropic effect of /9AR agonists (12), and sympathetic stimulation of renin secretion (13), so that defects could result in failure of the heart to adapt to an increased pressure load, increased peripheral resistance (6-9), and the low plasma renin seen in a large proportion of HT patients (14).Although the role of adrenoceptors in HT has been a subject of intense investigation by many groups, no study to date has addressed the important question of primary involvement of a variant of one of the adrenoceptor genes, nor of any other neural gene, in disease onset. In the present work we examined the a2-AR gene (ADRA2R) and the P1AR gene (ADRA1R), which share the same locus on chromosome 10 (q24-q26) (cf. the a l-and /92-adrenoceptor genes, which are located at chromosome 5831-q32) (15). MethodsStudy Design All subjects were adult Caucasian. HT patients were selected on the basis of correct diagnosis of essential HT in accord with conventional crite...

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Section: Discussionsupporting

confidence: 82%

Section: Rflp Analysesmentioning

confidence: 99%

Section: Rflp Analysesmentioning

confidence: 99%

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Association Analyses of RFLPs for the .ALPHA.2- and .BETA.1-Adrenoceptor Genes in Essential Hypertension.

1992

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“…Angiotensin-converting enzyme (ACE), an important component of the rennin-angiotensin system, regulates BP by activating an inactive angiotensin I (AT-I) into a potent vasopressor, angiotensin II (AT-II), and inactivating a potent vasodilator, bradykinin. 2 Since Rigat et al 3 identified a biallelic polymorphism in the ACE gene that is characterized by either the absence (deletion D) or presence (insertion I) of a 287-bp Alu repeat sequence, several studies have shown an association of ACE genotype with BP, 4,5 whereas other studies have not. [6][7][8] G-protein is a heterotrimeric protein that consists of a-, b-, and gsubunits.…”

Section: Introductionmentioning

confidence: 99%

GNB3 gene C825T and ACE gene I/D polymorphisms in essential hypertension in a Kazakh genetic isolate

Wang

Lin

et al. 2004

J Hum Hypertens

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The Kazakh inhabitants living in Barkol pasture of northeast China belong to a genetic isolate characterized by ethnically homogeneous and a communal pastoral lifestyle. To investigate whether the polymorphisms in the G-protein b-3 subunit (GNB3) gene and angiotensin-converting enzyme (ACE) gene are associated with essential hypertension (EH), we carried out a case-control study of 290 hypertensive subjects and 244 normotensive (NT) controls randomly selected from Kazakh populations of Barkol. A previous medical history of diabetes and hypertension, and body mass index (BMI) was recorded. Plasma glucose, triglyceride, and cholesterol were measured. The insertion/deletion (I/D) polymorphism of the ACE gene and the C825T polymorphism of the GNB3 gene were determined by the polymerase chain reaction (PCR) technique. The distributions of genotypes and alleles for the two polymorphisms did not differ significantly between the case and control populations, and odds ratio of EH related to the ACE gene D allele and GNB3 gene T allele was not significantly different from 1.0. Logistic regression analysis shows the variation at the GNB3 and ACE did not have any statistically significant synergistic effect on blood pressure (BP). Stratification of NT and untreated hypertensives according to I/D polymorphism of ACE gene and C825T polymorphism of GNB3 gene disclosed no significant difference across genotypes with respect to BMI, glucose, triglyceride, cholesterol, systolic and diastolic BP. In conclusion, the polymorphisms in the GNB3 gene and ACE gene, solely or combined, did not confer a significantly increased risk for the development of EH in the Kazakh isolate of northeast China.

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“…A first study by Zee et al [85] demonstrated a higher I allele frequency in hypertensive patients with a family history of hypertension. However, several similar studies failed to show any significant relation between high blood pressure and the ACE genotype (see Table 3).…”

Section: Hypertensionmentioning

confidence: 99%

Aspects of gene polymorphisms in cardiovascular disease: the renin‐angiotensin system

Carluccio

Soccio

Caterina

2001

Eur J Clin Investigation

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The renin-angiotensin system (RAS) plays a central role in cardiovascular homeostasis. Angiotensin is the key peptide of the RAS, and exerts its influence on the heart and blood vessels both through its haemodynamic effects (via its influence on after-load and pre-load and determining coronary vasoconstriction) and through its direct cellular effects (via its actions on cell proliferation). Numerous studies in the past 10 years have demonstrated that the pharmacological inhibition of angiotensin converting enzyme (ACE), one of the two critical enzymes of the RAS, improves the outcome in patients with several cardiovascular disorders (hypertension, heart failure, ischaemic heart disease). These studies suggest a role of the RAS as a major determinant of cardiovascular risk. Recent data suggest that genetics may in turn contribute to modulating the effects of angiotensin on coronary vascular biology and ischaemia. This paper reviews the physiologic characteristics of the RAS and recent research developments related to angiotensin cell biology and pathobiology in heart disease. In particular, this review will cover the genetic aspects of RAS and their implications in cardiovascular disease.

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Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension

Cited by 249 publications

References 18 publications

Association Analyses of RFLPs for the .ALPHA.2- and .BETA.1-Adrenoceptor Genes in Essential Hypertension.

Association Analyses of RFLPs for the .ALPHA.2- and .BETA.1-Adrenoceptor Genes in Essential Hypertension.

GNB3 gene C825T and ACE gene I/D polymorphisms in essential hypertension in a Kazakh genetic isolate

Aspects of gene polymorphisms in cardiovascular disease: the renin‐angiotensin system

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