Angiotensin Converting Enzyme (ACE)
The major regulator of mineralocorticoid synthesis is the
renin/angiotensin system. Angiotensin converting enzyme (ACE)
converts angiotensin I to angiotensin II, a potent vasoconstrictor and
stimulator of aldosterone secretion by the adrenal gland.
High circulating plasma ACE is associated with high circulating levels of
PAI-1 (plasminogen activator inhibitor-1), the major inhibitor of
fibrinolysis in the circulation.
There is an insertion/deletion (I/D) of a 287 bp fragment within intron
16 in the ACE gene the allele frequency of which is I=44% and D=56%.
Assuming simple Mendelian inheritance, the genotype frequencies (in
Caucasians) would be: D/D= 36%, D/I=40% and I/I=24%.
The plasma ACE concentration (in IU/L)in patients with the D allele is
higher than that in patients with the I allele, e.g., D/D= 18 IU, D/I= 14.5
IU, and I/I 11.0 IU.
The D/D genotype is associated with left ventricular hypertrophy
(LVH), with or without hypertension, odds ratio = 2.63 at 95%
confidence
The D allele is associated with myocardial infarction, increased plaque
instability, stent restenosis, LVH, ischemic or idiopathic
cardiomyopathy, coronary artery disease, and other cardiovascular
diseases, including diabetes mellitus and diabetic nephropathy.
ACE may modulate, either directly or indirectly, the above
cardiovascular diseases. Thus ACE inhibitors may have advantages
over other antihypertensive drugs.
High circulating plasma ACE is associated with high circulating levels of
PAI-1 (plasminogen activator inhibitor-1), the major inhibitor of
fibrinolysis in the circulation.
References:
1. Schunkert, H., et al., (1994) Association between a deletion
polymorphism of the angiotensin-converting-enzyme gene and left
ventricular hypertrophy. New Eng. J. Med. 330:1634-1638.
2. Abbud, Z. A. et al., (1998) Angiotension-Converting Enzyme Gene
Polymorphism in Systemic Hypertension. Am. J. Cardio. 81-244-246
3. Kario, K. et al. (1997) Hypertension nephropathy and the gene for
angiotensin-converting enzyme. Arterio., Thromb. Vas. Biol.
17:252-256
4. Nakano, Y. et al. (1997) Angiotensin I-converting enzyme gene
polymorphism and acute response to Captopril in essential
hypertension. Am. J. Hyperten. 10:1064-1068.
5. O’Malley, J. P. et al. (1998) Angiotensin-converting enzyme DD
genotype and cardiovascular disease in Heterozygous Familial
Hypercholesterolemia. Circulation 97:1780-1783
6. Ribichini, F. et al. (1998) Plasma activity and insertion/deletion
polymorphism of angiotensin I-converting enzyme. A major risk factor
and a marker of risk for coronary stent restenosis. Circ. 97:147-154.
7. Ohmichi, N. (1997) Relationship between the response to the
angiotensin converting enzyme inhibitor Imidapril and the angiotensin
converting enzyme genotype. Am. J. Hyperten. 10:951-955
8. Mondorf, U. F. et al. (1998) Contribution of angiotensin I converting
enzyme gene polymorphism and angiotensinogen gene polymorphism
to blood pressure regulation in essential hypertension. Am. J.
Hyperten. 11:174-183.
9. van Essen, G. G., et al. (1996) Association between
angiotensin-converting-enzyme gene polymorphism and failure of
renoprotective therapy. The Lancet 347:94-95.
10. Kim, Duk-Kyung, et al. (1997) Polymorphism of angiotensin
converting enzyme gene is associated with circulating levels of
plasminogen activator inhibitor-1. Arterio., Thromb. Vas. Biol.
17:3242-3247.
11. Jacobsen, P. et al. (1998) Angiotensin converting enzyme gene
polymorphism and ACE inhibition in diabetic nephropathy. Kidney
International 53:1002-1006.
For more information go to National Center for Biotechnology Information
(NCBI). Most abstracts and many full length articles can be printed from this
web site.
|
