Angiotensin-Converting Enzyme
            <i>I/D</i>
            Polymorphism and Arterial Wall Thickness in a General Population

Castellano, Maurizio; Muiesan, María Lorenza; Rizzoni, Giorgio; Beschi, Marina; Pasini, Gianfranco; Cinelli, Angel R.; Salvetti, Massimo; Porteri, Enzo; Bettoni, Giorgio; Kreutz, Reinhold; Lindpaintner, Klaus; Rosei, Enrico Agabiti

doi:10.1161/01.cir.91.11.2721

Cited by 124 publications

(78 citation statements)

References 17 publications

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“…68 In accordance with this, a high expression of ACE was associated with a statistically significant increase in common carotid artery intima-media thickening, 69 and an association between DD genotype and the extent of common carotid artery intima-media thickening has been reported. 70 Those clinical data are concordant with our experimental results.…”

Section: Discussionsupporting

confidence: 86%

Angiotensin I-Converting Enzyme Genotype Influences Arterial Response to Injury in Normotensive Rats

Challah

Villard

Philippe

et al. 1998

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Abstract-Two normotensive strains of rat, the Lou and Brown Norway (BN) strains, have contrasting levels of plasma angiotensin-converting enzyme (ACE). To investigate the degree of genetic determination of ACE expression, a polymorphic marker of the ACE gene was analyzed in inbred rats of the two strains. The two inbred strains were shown to bear different alleles for a polymorphic marker at the ACE gene. The segregation of the alleles of this marker and the plasma ACE levels were studied in a group of F2 rats issued from a cross between Lou and BN rats. The degree of genetic determination of plasma ACE activity was estimated to be 94% in the F2 cohort. The ACE locus accounts for 74% of total plasma ACE variance. ACE activity and mRNA expression in lungs were also genetically determined. The difference observed in ACE mRNA accumulation in the lungs between the two strains was due to a difference in the transcriptional rate of the ACE gene, as shown in nuclear run-on experiments. No differences were observed in arterial blood pressure of homozygous F2 progeny. In these animals, ACE genotype did not interfere with the pressor or the depressor responses to ACE-dependent vasoactive peptides. There was a significant effect of strain on constitutive or inducible membrane or soluble ACE activity in primary cultures of vascular cells. Neointima formation in the carotid artery 14 days after balloon injury was also influenced by the genotype in F2 homozygous progeny, whereas the medial area was not. These results demonstrate that there is a close relationship between the genetically determined ACE expression and the inducibility of the ACE gene. The degree of genetic determination of ACE expression in inbred rat strains offers a unique opportunity to study the interaction between genetic and environmental determinants of ACE expression and its involvement in response to experimental cardiovascular and renal injury. (Arterioscler Thromb Vasc Biol. 1998;18:235-243.)

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Section: Discussionsupporting

confidence: 86%

Angiotensin I-Converting Enzyme Genotype Influences Arterial Response to Injury in Normotensive Rats

Challah

Villard

Philippe

et al. 1998

ATVB

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“…2 The same limitations appear to apply to the small number of studies that have examined the association of ACE I/D polymorphism with carotid IMT, and reported similarly heterogeneous findings (summarized in Table 5). [11][12][13][14][15][16] Four of these studies found a positive association, 11,14 -16 although this was only after a quarter of subjects on drug treatment were excluded from analysis in 1 small study 11 and only among nonsmokers in another study 16 ; 2 other studies 12,13 showed no association of the D allele with carotid wall thickening or disease despite that it conferred an increased risk of lacunar stroke in 1 study. 13 None of the studies were able to demonstrate a relationship between the D allele and carotid plaque or stenosis.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14][15][16] We therefore decided to test for the association of carotid IMT and ACE I/D polymorphism in the Perth Carotid Ultrasound Disease Assessment Study (CUDAS). The latter consisted of 1111 male and female subjects, aged 27 to 77 years, randomly selected from the Perth community population, all of whom had high-resolution bilateral B-mode carotid ultrasound examination and ACE I/D gene polymorphism determined as part of a detailed risk factor assessment.…”

mentioning

confidence: 99%

Angiotensin-Converting Enzyme Gene Polymorphism and Carotid Wall Thickening in a Community Population

Hung

McQuillan

Nidorf

et al. 1999

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Abstract-The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with an increased risk of coronary heart disease, but whether it is a risk factor for underlying atherosclerosis remains unclear. Therefore, we examined to see whether the ACE gene deletion polymorphism was associated with carotid wall thickening and atherosclerotic plaque formation in a large randomly selected community population. A total of 1111 subjects, aged 27 to 77 years, with an equal male:female ratio and equal numbers in each age decile, were randomly selected from the Perth community population. Mean common carotid intima-medial wall thickness (IMT) and focal plaque formation were assessed by high-resolution B-mode ultrasound.

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“…The ACE I/D polymorphism has been linked to various functional effects, for example the DD genotype being associated with high plasma ACE levels in addition to numerous diseases. One of the most extensively studied associations is with cardiovascular diseases, including myocardial infarction (Cambien et al, 1992 ;Nakai et al, 1994), left ventricular hypertrophy and dysfunction (Schunkert et al, 1994), dilated cardiomyopathy (Raynolds et al, 1993;Harn et al, 1995) hypertrophic cardiomyopathy (Marian et al, 1993), carotid thickening (Castellano et al, 1995;Kauma et al, 1996), venous thrombosis (Philipp et al, 1998), nephropathy (Schmidt & Ritz, 1997) and coronary restenosis after stent implantation (Amant et al, 1997). Currently, the best evidence for an association with the ACE I/D polymorphism is with arterial hypertension in men (Fornage et al, 1988 ;Higaki et al, 2000) ; one study of male carriers of the DD genotype showed a 1 .…”

Section: Introductionmentioning

confidence: 99%

The geographic distribution of the ACE II genotype: a novel finding

2007

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SummaryAngiotensin converting enzyme (ACE) gene polymorphism insertion (I) or deletion (D) has been widely studied in different populations, and linked to various functional effects and associated with common diseases. The purpose of the present study was to investigate the relationship between the ACE I/D frequency in different populations and geographic location; ACE I/D allele frequency in the Lebanese population and ACE II genotype contribution to the geographic trend were also identified. Five hundred and seventy healthy volunteers were recruited from the Lebanese population. Genomic DNA was extracted from buccal cells, and amplified by polymerase chain reaction; products were then identified by gel electrophoresis. The frequencies of the different ACE I/D genotypes were determined and tested for Hardy-Weinberg equilibrium (HWE). To assess the relationship between ACE I/D frequency and geographic location, and to identify how the Lebanese population contributes to the geographic trend in ACE I/D frequencies, Eurasian population samples and Asians were incorporated in the analyses from the literature. The frequency of the I allele in the Lebanese population was 27% and the corresponding II genotype was at a frequency of 7 . 37% (in HWE ; P=0 . 979). The ACE I allele and genotype frequencies show an association with longitude, with frequencies increasing eastwards and westwards from the Middle East.

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Angiotensin-Converting Enzyme I/D Polymorphism and Arterial Wall Thickness in a General Population

Abstract: ACE DD genotype may be considered a risk factor for the development of common carotid intima-media thickening in our study population.

Cited by 124 publications

References 17 publications

Angiotensin I-Converting Enzyme Genotype Influences Arterial Response to Injury in Normotensive Rats

Angiotensin I-Converting Enzyme Genotype Influences Arterial Response to Injury in Normotensive Rats

Angiotensin-Converting Enzyme Gene Polymorphism and Carotid Wall Thickening in a Community Population

The geographic distribution of the ACE II genotype: a novel finding

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