A DNA Variant at the Angiotensin-Converting Enzyme Gene Locus Associates With Coronary Artery Disease in the Caerphilly Heart Study

Mattu, Raj K.; Needham, Ewa; Galton, D. J.; Frangos, E; Clark, Adrian; Caulfield, M

doi:10.1161/01.cir.91.2.270

Cited by 151 publications

(85 citation statements)

References 35 publications

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“…12 Since that time a lot of studies were performed in which ACE genotype was used as a tool, through association studies, to investigate the role of tissue ACE in human disease pathogenesis. [13][14][15][16][17] Taken together, the available evidence supports the notion that the DD ACE genotype adversely influences specific cardiovascular diseases but appears to do so in specific geographical areas and in particular patient subgroups. 18 This can be a possible explanation of the inconsistency of association between ACE genotype and ED.…”

Section: Introductionsupporting

confidence: 62%

Association between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and erectile dysfunction in patients with metabolic syndrome

et al. 2007

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This study was designed to investigate whether angiotensin-converting enzyme (ACE) insertion/ deletion (I/D) polymorphism is associated with erectile dysfunction (ED) in Russian men with metabolic syndrome (MS). A total of 331 men with MS were studied. All patients underwent complex evaluation including the International Index of Erectile Function (IIEF) questionnaire. The ACE I/D polymorphism was determined by polymerase chain reaction. Overall, 182 men (55.0%) had ED according to the IIEF erectile function domain score. In the ED group, the prevalence of DD genotype was found to be significantly higher compared to the non-ED group (Po0.001). In both groups, patients with DD genotype were significantly younger than patients with other genotypes (Po0.001). In addition, in the ED group, the disease affected patients with DD genotype at a significantly younger age (Po0.001). Obtained results give evidence to support the finding that the D allele is a risk factor for the micro-and macrovascular diseases.

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Section: Introductionsupporting

confidence: 62%

Association between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and erectile dysfunction in patients with metabolic syndrome

et al. 2007

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“…4,38 In contrast, the data that support the contention that the D allele could also be a general marker of CVD are controversial. Positive studies [7][8][9][10][11][12][13][14] have in fact been contradicted not only by negative results basically for all types of CVD [15][16][17][18] (for reviews, see Koch et al 19 and Samani et al 45 ) but also by a study showing an association of the D allele with longevity in centenarians. 46 The mechanisms responsible for the supposed predisposition to developing CVD also remain largely speculative, because (1) the D/I polymorphism is located in intron 16 (ie, a noncoding region); (2) no change in the kinetic properties of ACE in relation with this polymorphism was documented 47 ; and (3) the contention that the higher ACE plasma levels associated with the D allele enhances Ang II generation in vivo 31 has been challenged.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 The D allele has thereafter been associated with other CVD, including dilated and ischemic cardiomyopathy, coronary and carotid artery disease, coronary artery spasm, restenosis, left ventricular hypertrophy in hypertensives, left ventricular dysfunction, and, more recently, atherosclerotic renovascular hypertension. [7][8][9][10][11][12][13][14] However, opposite results for almost every clinical association have also been published, and therefore the value of the D/I genotyping for the purpose of cardiovascular risk stratification has been challenged [15][16][17][18][19][20][21][22][23] (for reviews, see Butler et al 24 and Agerholm-Larsen et al 25 ). Furthermore, the mechanisms by which the D allele would lead to a generalized increase in CVD risk remain largely speculative.…”

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confidence: 99%

Exclusion of the ACE D/I Gene Polymorphism as a Determinant of Endothelial Dysfunction

et al. 2001

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Abstract-A deletion/insertion (D/I) polymorphism within the ACE gene may increase the risk of cardiovascular events through still unknown mechanisms. The latter may involve increased angiotensin II-induced NO breakdown and/or reduced agonist-mediated NO release. We therefore investigated whether the D allele of the ACE gene affects endothelium-dependent vasodilatation in mild-to-moderate primary hypertensive patients and healthy normotensive subjects. We compared in a cross-sectional study the forearm blood flow response of the 3 D/I genotypes with 5 incrementally increasing doses of the endothelium-dependent vasodilator acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 g ⅐ 100 mL Ϫ1 ⅐ min Ϫ1) in 142 subjects: 103 mild-to-moderate uncomplicated primary hypertensives (49.3Ϯ9.1 years old, 152Ϯ11/99Ϯ5 mm Hg) and 39 normotensives (44.6Ϯ15.3 years old, 122Ϯ12/78Ϯ6 mm Hg). We also assessed the endothelium-independent vasodilatation in the forearm, as blood flow response to 3 incrementally increasing doses of sodium nitroprusside (1, 2, and 4 g ⅐ 100 mL Ϫ1 ⅐ min Ϫ1 ). The overall genotype distribution was II, nϭ10; ID, nϭ70; and DD, nϭ62. It did not differ significantly between primary hypertensives and normotensives. A significant blunting of endothelium-dependent vasodilatation in primary hypertensive patients compared with normotensive subjects (PϽ0.001) was found. No effect of the DI genotype on endothelium-dependent and -independent vasodilatation was detected. Thus, these results obtained in a relatively large population do not support the contention that the D allele is associated with a blunting of either stimulated endothelial NO or donated NO responses in both mild-to-moderate primary hypertensive patients and normotensive subjects. (Hypertension. 2001;37:293-300.)

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“…These findings have also been shown in other populations, even in prospective studies. 10,11 However, not all studies have demonstrated this association. 12,13 There are few studies that have investigated the association between BMI, ACE gene I/D polymorphism and CHD.…”

Section: Introductionmentioning

confidence: 99%

“…12,13 There are few studies that have investigated the association between BMI, ACE gene I/D polymorphism and CHD. 10,13 In Mediterranean populations in Southern Europe with a low incidence and prevalence of CHD, the commented relation has not been studied.…”

Section: Introductionmentioning

confidence: 99%

The relation between obesity, abdominal fat deposit and the angiotensin-converting enzyme gene I/D polymorphism and its association with coronary heart disease

Riera-Fortuny

Real

Chaves³

et al. 2004

Int J Obes

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OBJECTIVE:To analyse the relation between overweight, obesity and fat distribution with I/D polymorphism of the angiotensinconverting enzyme (ACE) gene and its association with coronary heart disease (CHD). DESIGN: Cross-sectional, case-control study. SUBJECTS: A total of 185 cases (141 males) who had suffered at least one episode of CHD and 182 controls (127 males). MEASUREMENTS: Body mass index, waist circumference, blood pressure, plasma total cholesterol, triglycerides, HDL cholestrol and fasting glucose were measured with standard methods, genotyping the I/D polymorphism of ACE gene. RESULTS: Obesity and abdominal fat deposit are associated with CHD in women, but not independently. We have found an association between obesity and abdominal fat deposit with the ACE gene I/D polymorphism in subjects with CHD. Subjects with CHD and DD or ID genotypes have significantly higher prevalence of obesity and abdominal fat deposit and higher values of weight and waist circumference. In addition, the DD and ID genotypes increased crude OR of obesity. The DD and ID genotypes of the ACE gene I/D polymorphism and BMI are independently associated with CHD. CONCLUSION: There is a relation between the type and grade of obesity with the genotypes of the ACE gene I/D polymorphism in subjects with CHD.

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A DNA Variant at the Angiotensin-Converting Enzyme Gene Locus Associates With Coronary Artery Disease in the Caerphilly Heart Study

Abstract: The DD genotype is a linkage marker for an etiologic mutation at or near the ACE gene that may confer risk of CAD detectable in subjects previously unidentifiable with "classic" risk factors. However, this risk may be quantitatively small among the general male population.

Cited by 151 publications

References 35 publications

Association between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and erectile dysfunction in patients with metabolic syndrome

Association between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and erectile dysfunction in patients with metabolic syndrome

Exclusion of the ACE D/I Gene Polymorphism as a Determinant of Endothelial Dysfunction

The relation between obesity, abdominal fat deposit and the angiotensin-converting enzyme gene I/D polymorphism and its association with coronary heart disease

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