ACE I/D gene polymorphism: presence of the ACE D allele increases the risk of coronary artery disease in younger individuals

Gardemann, Andreas; Fink, Monika; Stricker, Jürgen; Nguyên, Quôc Dinh; Humme, Jörg; Katz, Norbert; Tillmanns, Harald; Hehrlein, F. W.; Rau, Matthias; Haberbosch, Werner

doi:10.1016/s0021-9150(98)00040-9

Cited by 70 publications

(53 citation statements)

References 42 publications

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“…Thus, we may be left with a population that is less susceptible to cardiovascular diseases. Indeed, Gardemann et al 45 found, in 2267 white males, an association of the D allele with coronary artery disease in subjects younger than 61.7 years of age but not in subjects aged 61.7 years or older.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study

Nicklas

Pahor

et al. 2007

J Hum Hypertens

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The role of renin-angiotensin system (RAS) genes on the risk of lower extremity arterial disease (LEAD) in elderly people remains unclear. We assessed the relationship of genetic polymorphisms in RAS: G-6A, T174M and M235T of the angiotensinogen (AGT) gene, and the angiotensin-converting enzyme insertion/deletion (ACE_I/D) variant to the risk of LEAD in the Health, Aging and Body Composition (Health ABC) Study. This analysis included 1228 black and 1306 white men and women whose age ranged between 70 and 79 years at the study enrollment. LEAD was defined as ankle-arm index (AAI) o0.9. Genotype-phenotype associations were estimated by regression analyses with and without adjustment for established cardiovascular disease (CVD) risk factors. The proportion of LEAD was significantly higher in black (21.1%) than that in white elderly people (10.1%, Po0.0001). The distribution of AGT polymorphisms was also significantly different between black and white participants. There was no statistically significant association between the selected RAS genetic variants and LEAD after adjustment for age, antihypertensive medications, lipid-lowering medication, pack-year smoking, body mass index, low-density lipoprotein cholesterol, and prevalent diabetes and coronary heart disease. However, A-T haplotype of G-6A and M235T interacting with homozygous ACE_II (b ¼ À1.07, P ¼ 0.006) and with ACE inhibitors (b ¼ À1.03, P ¼ 0.01) significantly decreased the risk of LEAD in white but not in black participants after adjustment for the selected CVD risk factors. In conclusion, the study observed a gene-gene and gene-drug interaction for LEAD in the white elderly.

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Section: Discussionmentioning

confidence: 99%

Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study

Nicklas

Pahor

et al. 2007

J Hum Hypertens

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“…The D-allele of the ACE I/Dpolymorphism has been associated with arterial hypertension 46,47 and the risk of left ventricular hypertrophy, 48 and may be associated with the risk of coronary artery disease. 49 In addition, depression appears to be a risk factor for both morbidity and mortality of coronary heart disease, 50,51 and significantly increases mortality after survival of a myocardial infarction. 52,53,54 On the other hand, depression is also a predisposing factor for coronary heart disease.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the angiotensin-converting enzyme gene are associated with unipolar depression, ACE activity and hypercortisolism

et al. 2006

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Angiotensin-converting enzyme (ACE) is assumed to influence the activity of the hypothalamic-pituitary-adrenocortical (HPA) system, which shows hyperactivity in the majority of patients with major depression. The ACE gene, known to be associated with cardiovascular disorders, which in turn are accompanied with an increased susceptibility for depression, is therefore a promising candidate gene for affective disorders. We investigated the genetic association between 35 single-nucleotide polymorphisms (SNPs) and an insertion/deletion (I/D)-polymorphism in the ACE gene and the susceptibility for unipolar major depression together with the genetic association with ACE serum activity and functional parameters of the HPA system. Two independent case/control samples with a total of 843 unrelated unipolar depressed patients and 1479 healthy controls were investigated. A case/control sample was screened to detect genetic associations with unipolar major depression. In addition, a replication sample was used to confirm the detected associations and to further investigate functional consequences of the genetic variants associated with depression. In the screening sample, two SNPs within the ACE gene were significantly associated with unipolar major depression. The association with unipolar major depression of one SNP (rs4291) located in the promoter region of the ACE gene was confirmed in our replication sample. The T-allele of this SNP was associated with depression and depressed T-allele carriers showed higher ACE serum activity and HPA-axis hyperactivity. Variants of the ACE gene such as SNP rs4291 are suggested susceptibility factors for unipolar major depression. We could show that SNP rs4291 influences ACE activity and HPA-axis hyperactivity and might therefore represent a common pathophysiologic link for unipolar depression and cardiovascular disease.

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“…The density of myocardial AT 2 receptors was demonstrated to be increased in experimental myocardial infarction and in cardiomyopathic hamsters [33]. AT 2 receptors are reported to be upregulated in cardiac fibroblasts in fibrous regions of Case-referent ± / ± Agerholm-Larsen [57] 170 7263 Retrospective ± / ± Gardemann [60] 384 678 Case-control 1 / ± Biggard [58] 101(, 55ys) 100 Case-control ± / 1 Arca [59] 236 158 Case-control ± / ± Jeuinemaitre [54] 156 207 Cross-sectional ± / ± human hearts, exerting an effect contrasting the action of the AT 1 receptors on the progression of interstitial fibrosis during cardiac remodelling. Via AT 2 receptors, Ang II has been recognised to inhibit both fibrillar collagen metabolism and the growth of cardiac fibroblasts [34,35].…”

Section: Ang II In Left Ventricular Dysfunction Due To Coronary Artermentioning

confidence: 99%

“…After the above-mentioned meta-analysis, a few additional studies have investigated the relevance of the ACE I/D trait with respect to ischaemic heart disease [54,57±60], but only one of these studies reported a positive association between the D allele and coronary events [60] ( Table 2). …”

Section: The Ace I/d Polymorphism and Ischaemic Heart Disease: Furthementioning

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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ACE I/D gene polymorphism: presence of the ACE D allele increases the risk of coronary artery disease in younger individuals

Cited by 70 publications

References 42 publications

Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study

Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study

Polymorphisms in the angiotensin-converting enzyme gene are associated with unipolar depression, ACE activity and hypercortisolism

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

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