Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

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
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 20
Specimen type genomic DNA
Clinic Method Target mutation analysis
Turnaround 20
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25
Specimen type genomic DNA

Related Diseases:

Diabetic nephropathy
ACE
AGT
AKR1B1
Hypertension
ACE
ACE2
AGT
Benign hyperproreninemia
REN
Monogenic hypertension
Apparent mineralocorticoid excess
HSD11B2
Glucocorticoid triggered hypertension
NR3C1
Hyperaldosteronism
Conn syndrome
ATP1A1
ATP2B3
CACNA1D
CACNA1H
CTNNB1
KCNJ5
Glucocorticoid triggered hypertension
NR3C1
Hyperaldosteronism type 1
CYP11B1
CYP11B2
Hyperaldosteronism type 2
Hyperaldosteronism type 3
KCNJ5
Hyperaldosteronism type 4
CACNA1D
CACNA1H
Hypertension and brachydactyly syndrome
PDE3A
Liddle syndrome
NEDD4
NEDD4L
NR3C2
OXSR1
SCNN1B
SCNN1G
STK39
Pseudohypoaldosteronism
Pseudohypoaldosteronism type 2
CUL3
KLHL3
WNK1
WNK4
Pseudohypoaldosteronism type1
NR3C2
SCNN1A
SCNN1B
SCNN1G
Preeclampsia
APOL1
Preeclampsia 1
Preeclampsia 2
Preeclampsia 3
Preeclampsia 4
STOX1
Preeclampsia 5
CORIN
Salt-sensitive essential hypertension
CYP3A5
VEGFC
Renal tubular dysgenesis
ACE
AGT
AGTR1
REN

References:

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2.

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Vleming LJ et al. (1999) The DD genotype of the ACE gene polymorphism is associated with progression of diabetic nephropathy to end stage renal failure in IDDM.

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9.

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48.

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62.

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63.

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64.

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65.

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66.

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67.

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68.

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Update: Sept. 26, 2018