ACE-gen polymorphism and cardiovascular diseases

Klinik und Poliklinik für Innere Medizin II, Universität Regensburg.
Herz (Impact Factor: 0.69). 03/2000; 25(1):1-6. DOI: 10.1007/BF03044118
Source: PubMed


The angiotensin converting enzyme (ACE) is an integral part of enzymatic cascades leading to generation of angiotensin II as well as degradation of bradykinin. For this reason, it represents an important part for the metabolism of 2 vasoactive peptides. Early in this decade, convincing experimental evidence demonstrated the induction of this enzyme in several pathophysiological conditions including myocardial infarction and left ventricular hypertrophy. In parallel, a deletion/insertion (D/I) polymorphism of the human ACE gene was discovered that was related to 14 to 50% of the interindividual variance of serum ACE activity. More recently, this polymorphism was implicated in the pathogenesis of a variety of cardiovascular disorders including myocardial infarction, left ventricular hypertrophy, hypertension as well as nephropathy.
The genotyping of more than 100,000 patients for this polymorphism showed that some of theses conditions establish a low but sometimes inconsistent relation to the deletion allele. These inconsistent results might be caused either by further polymorphisms of the ACE-gene (so far 78 such DNA variants are known) or by polymorphisms of other components or the negative feedback regulation of the renin angiotensin system. Therefore, the pathopysiological situation is much more complex as initially presumed.
This paper intends to reflect the current evidence on the relation between the ACE deletion/insertion polymorphism and cardiovascular diseases.

3 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.
    Full-text · Article · Nov 2001 · The American Journal of Cardiology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Definition of the problem: Recent progress in the pharmacological sciences provides a first glimpse of the development of an individual, genotype-based drug therapy in order to improve the efficiency of drug utilization. Genotyping of genetic polymorphisms in genes involved in drug response promises to optimize drug therapy fundamentally by identifying patients for whom a pharmaceutical agent may be effective and safe or contraindicated because of expected adverse drug reactions. Arguments: The new pharmacogenomic treatment strategies raise complex bioethical issues, because genetic screening for drug therapy may identify asymptomatic patients who are at risk for a particular adverse outcome. Thus, pharmacogenomics will affect the relationship between the treating physician and the patient which is traditionally based on privacy, confidentiality, beneficience and non-maleficience. Conclusion: In the article presented some ethical aspects of these new pharmacogenomic approaches concerning the physician-patient relationship are discussed.
    No preview · Article · Feb 2002 · Ethik in der Medizin
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological observational studies have shown existing interindividual and interethnical differences in drug metabolism. This results in a great variety of effects and side effects of drugs. One reason for these variabilities are genetic polymorphisms which occur on the basis of single-nucleotide exchanges or insertional and deletional mutations. Such mutations may involve transport proteins or metabolizing enzymes of phase I and phase II reactions, as cytochrome P450, glucuronidases and enzymes which metabolize cytostatics. The differences in pharmacokinetics and pharmacodynamics have an impact on therapeutical outcome. Dosage adjustments should be undertaken before the initiation of therapy in reflection of modern genotyping. This is particularly important in oncology to avoid life-threatening adverse drug reactions. Examples of cardiovascular and neurological diseases are presented to demonstrate the impact of genetic polymorphisms on the incidence and prevalence of diseases as well as the responses to medications like beta blockers, ACE inhibitors and psychotropic drugs. Finally, additional factors are summarized, which may contribute to the large diversity of drug reactions.
    No preview · Article · Nov 2003 · Der Internist
Show more