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.

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