Scientific background:

Summary: This gene to be involved in hypertension, hypertensive complications, and diabetic nephropathy is discussed by several publications.

Gene: The gene of the angiotensin converting enzyme (ACE) is localized on chromosome 17 (17q23). Size is about 20kb. It consists of 25 exons.

Molecule: ACE is an enzyme, a zinc metalloendopeptidase that functions as a carboxyl directed dipeptidase.

Pathology: The function of the protein product of this gene is the conversion of angiotensin I to angiotensin II. The latter is a potent vasoconstrictor. The importance of ACE is in blood pressure regulation by the mean of the activation of angiotensinogen (AGT) wich is secreted as a prohormone. ACE fulfills the last step of activation. The gene exists in two different variants. One form is chracterized by additional 250bp in intron 16. This variant is called I (insertion) and it will be distinguished from D deletion. Because these changes are localized in the intron there is no direct influence expected on protein structure. But this polymorphism can have an influence on gene regulation or may be in linkage dysequilibrium with other more importen changes on the same gene.

Pathophysiology: ACE not only cleaves angiotensin I to angiotensin II, but also

Clinical signs: Hypertension is a very common disease. It is influenced by many genes. ACE polymorphism has an imoprtance in modifying the expression and maybe on renal and cardiac hypertensive injuries.

Epidemiology: This polymorphism is common wordwide. In general population the following allel frequencies are reported. DD 34% DI 44% II 22%

Interpretation: The higher frequency of D allel suggests that this had some benefit in past. But it seems that in modern times carier are more succeptable to the common diseases of modern countries. There is a doese dependent risk for cardiovascular disesase connected to the D allel.

Test strategy: Patients with hypertension with a known family risk for hypertensive injuries.

Methodology:

Literature: 

Nagel M, BMC Nephrol. 2005 Jan 11;6(1):1
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