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ACE I/D

Screening test for: Hypertension ACE (Angiotensin Converting Enzyme) is a zinc metallopeptidase abundantly distributed on the surface of endothelial cells and epithelial cells. It converts the inactive decapeptide Angiotensin I (Ang I or Ang 1-10) to active octapeptide Angiotensin II (Ang II or Ang 1-8) with potent vasoconstrictor. Ang II is the main active component of the renin-angiotensin system (RAS), which controls the blood pressure and blood volume in the body. ACE also plays an important role in kinin-kallikrein system as metabolizes bradykinin, which is a strong vasodilator in an inactive metabolite. ACE would, therefore, also involved in neurological diseases such as Parkinson’s disease, depression and other affective disorders. The ACE would also be able, in vitro, to demolish the beta-amyloid, implicated in the pathogenesis of Alzheimer’s disease.

The ACE gene is located on chromosome 17 (17q23.3) and comprises 26 exons and 25 introns. Plasma levels of ACE have a large inter-individual variability and in 1990 Rigat et al. identified a polymorphism involving the presence (insertion, I) or the absence (deletion, D) of an Alu sequence of 287 bp in the intron 16 of the gene. This polymorphism can produce, then, three different genotypes: a) II = Listing homozygous b) ID = Heterozygous for Insertion / Deletion c) DD = homozygous deletion. The level of enzyme activity in patients with ACE DD genotype was found to be twice as much as those who had a genotype II. Individuals with ID genotype had intermediate levels instead. Polymorphism I / D was responsible for about 47% of the observed variance in the levels of ACE in the current study. This study was confirmed not only on plasma levels of ACE, but also on the tissue. Polymorphism I/D ACE, and in particular D allele, although perfectly correlated with the levels of circulating ACE (intermediate phenotype), is loosely associated with the high blood pressure, while an association was confirmed with atherosclerosis, and in particular with the thickness of intimate of carotid artery.

In general, with regard to the association of D allele with cardiovascular disease and stroke, it is believed that it may play a role in selected groups of patients, particularly in those who already have other cardiovascular risk factors. Was rather demonstrated a significant association between the D allele and diabetic nephropathy (OR: 1.28), while the allele I has been associated with increased physical resistance to the effort, being the most responsible D allele of left ventricular hypertrophy from sports, to a lower metabolic efficiency of the heart muscle. Again, the I allele has been associated with Alzheimer’s disease (OR: 2.43) for the ability degrading the beta amyloid by the enzyme ACE. The β-blockers, finally, seem particularly suitable for cardiac patients homozygous for the D allele, because in them is preponderant influence of the renin - angiotensin system in the determination of cardiovascular disease. The kit is available in sizes from 24, 48 or 72 reactions.

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