angiotensin I-converting enzyme

The ACE gene to be involved in hypertension, hypertensive complications, and diabetic nephropathy is discussed by several publications.

Epidemiology

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

Gene Structure

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

Protein Structure

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

Phenotype

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.

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.

Gene Regulation

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

Test Strategy

Patients with hypertension with a known family risk for hypertensive injuries.

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.

Genetests:

Clinic	Method	Carrier testing
	Turnaround	5 days
	Specimen type	genomic DNA

Clinic	Method	Massive parallel sequencing
	Turnaround	25 days
	Specimen type	genomic DNA

Clinic	Method	Genomic sequencing of the entire coding region
	Turnaround	20 days
	Specimen type	genomic DNA

Clinic	Method	Target mutation analysis
	Turnaround	20 days
	Specimen type	genomic DNA

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