The ACE gene to be involved in hypertension, hypertensive complications, and diabetic nephropathy is discussed by several publications.
This polymorphism is common wordwide. In general population the following allel frequencies are reported. DD 34% DI 44% II 22%
The gene of the angiotensin converting enzyme (ACE) is localized on chromosome 17 (17q23). Size is about 20kb. It consists of 25 exons.
ACE is an enzyme, a zinc metalloendopeptidase that functions as a carboxyl directed dipeptidase.
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.
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.
ACE not only cleaves angiotensin I to angiotensin II, but also
Patients with hypertension with a known family risk for hypertensive injuries.
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.
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 |
1. |
Pei Y et al. (1997) Association of angiotensinogen gene T235 variant with progression of immunoglobin A nephropathy in Caucasian patients. |
2. |
Gribouval O et al. (2005) Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. |
3. |
Lalouel JM et al. (2001) Angiotensinogen in essential hypertension: from genetics to nephrology. |
4. |
Lovati E et al. (2001) Genetic polymorphisms of the renin-angiotensin-aldosterone system in end-stage renal disease. |
7. |
Chaves FJ et al. (2004) Polymorphisms of the renin-angiotensin system influence height in normotensive women in a Spanish population. |
8. |
Schächter F et al. (1994) Genetic associations with human longevity at the APOE and ACE loci. |
9. |
Yoshida H et al. (1995) Role of the deletion of polymorphism of the angiotensin converting enzyme gene in the progression and therapeutic responsiveness of IgA nephropathy. |
10. |
Julier C et al. (1997) Genetic susceptibility for human familial essential hypertension in a region of homology with blood pressure linkage on rat chromosome 10. |
11. |
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. |
12. |
Yoshioka T et al. (1998) Deletion polymorphism of the angiotensin converting enzyme gene predicts persistent proteinuria in Henoch-Schönlein purpura nephritis. |
13. |
Jeffery S et al. (1999) A dominant relationship between the ACE D allele and serum ACE levels in a Ghanaian population. |
14. |
Hu J et al. (1999) Angiotensin-converting enzyme genotype is associated with Alzheimer disease in the Japanese population. |
15. |
Williams AG et al. (2000) The ACE gene and muscle performance. |
17. |
Keramatipour M et al. (2000) The ACE I allele is associated with increased risk for ruptured intracranial aneurysms. |
18. |
Zhu X et al. (2000) Localization of a small genomic region associated with elevated ACE. |
19. |
Eyries M et al. (2001) Increased shedding of angiotensin-converting enzyme by a mutation identified in the stalk region. |
20. |
Alfalah M et al. (2001) A point mutation in the juxtamembrane stalk of human angiotensin I-converting enzyme invokes the action of a distinct secretase. |
21. |
Zhu X et al. (2001) Linkage and association analysis of angiotensin I-converting enzyme (ACE)-gene polymorphisms with ACE concentration and blood pressure. |
22. |
Exner DV et al. (2001) Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction. |
23. |
Woods D et al. (2001) Angiotensin-I converting enzyme genotype-dependent benefit from hormone replacement therapy in isometric muscle strength and bone mineral density. |
24. |
Kramers C et al. (2001) Point mutation in the stalk of angiotensin-converting enzyme causes a dramatic increase in serum angiotensin-converting enzyme but no cardiovascular disease. |
25. |
Hu J et al. (2001) Angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide (A beta ); retards A beta aggregation, deposition, fibril formation; and inhibits cytotoxicity. |
26. |
Huang W et al. (2001) Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse. |
27. |
Harding D et al. (2002) Severity of meningococcal disease in children and the angiotensin-converting enzyme insertion/deletion polymorphism. |
28. |
Hamdi HK et al. (2002) Alu DNA polymorphism in ACE gene is protective for age-related macular degeneration. |
29. |
Yoon HJ et al. (2002) Interdependent effect of angiotensin-converting enzyme and platelet-activating factor acetylhydrolase gene polymorphisms on the progression of immunoglobulin A nephropathy. |
30. |
Zhang B et al. (2002) Association of angiotensin-converting-enzyme gene polymorphism with the depressor response to mild exercise therapy in patients with mild to moderate essential hypertension. |
31. |
Harmer D et al. (2002) Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. |
32. |
Natesh R et al. (2003) Crystal structure of the human angiotensin-converting enzyme-lisinopril complex. |
33. |
Zhang B et al. (2003) The I allele of the angiotensin-converting enzyme gene is associated with an increased percentage of slow-twitch type I fibers in human skeletal muscle. |
34. |
Martinuzzi A et al. (2003) Phenotype modulators in myophosphorylase deficiency. |
35. |
Kehoe PG et al. (2003) Haplotypes extending across ACE are associated with Alzheimer's disease. |
36. |
Kessler SP et al. (2003) Maintenance of normal blood pressure and renal functions are independent effects of angiotensin-converting enzyme. |
37. |
Rigat B et al. (1992) PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). |
38. |
Tiret L et al. (1992) Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. |
39. |
None (1992) Myocardial infarction. The ACE of hearts. |
40. |
Cambien F et al. (1992) Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. |
41. |
Jeunemaitre X et al. (1992) Absence of linkage between the angiotensin converting enzyme locus and human essential hypertension. |
43. |
Harding D et al. (2003) Angiotensin-converting enzyme DD genotype is associated with worse perinatal cardiorespiratory adaptation in preterm infants. |
44. |
Linnebank M et al. (2003) Hereditary elevation of angiotensin converting enzyme suggesting neurosarcoidosis. |
45. |
Winnicki M et al. (2004) Physical activity and angiotensin-converting enzyme gene polymorphism in mild hypertensives. |
46. |
Elkins JS et al. (2004) Alzheimer disease risk and genetic variation in ACE: a meta-analysis. |
47. |
Kehoe PG et al. (2004) Common variants of ACE contribute to variable age-at-onset of Alzheimer's disease. |
48. |
Hamdi HK et al. (2004) A genetic variant of ACE increases cell survival: a new paradigm for biology and disease. |
49. |
Tian XL et al. (2004) Over-expression of angiotensin converting enzyme-1 augments cardiac hypertrophy in transgenic rats. |
50. |
Suehiro T et al. (2004) Increased amount of the angiotensin-converting enzyme (ACE) mRNA originating from the ACE allele with deletion. |
51. |
Slowik A et al. (2004) DD genotype of ACE gene is a risk factor for intracerebral hemorrhage. |
52. |
Kakoki M et al. (2004) Diabetic nephropathy is markedly enhanced in mice lacking the bradykinin B2 receptor. |
53. |
Katzov H et al. (2004) A cladistic model of ACE sequence variation with implications for myocardial infarction, Alzheimer disease and obesity. |
54. |
Itoyama S et al. (2004) ACE1 polymorphism and progression of SARS. |
55. |
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56. |
Casas JP et al. (2004) Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. |
57. |
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58. |
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60. |
Meng Y et al. (2006) Association of polymorphisms in the Angiotensin-converting enzyme gene with Alzheimer disease in an Israeli Arab community. |
61. |
Cooper WO et al. (2006) Major congenital malformations after first-trimester exposure to ACE inhibitors. |
62. |
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63. |
Jayasooriya AP et al. (2008) Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance. |
64. |
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65. |
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66. |
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67. |
Ehlers MR et al. (1989) Molecular cloning of human testicular angiotensin-converting enzyme: the testis isozyme is identical to the C-terminal half of endothelial angiotensin-converting enzyme. |
68. |
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69. |
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71. |
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72. |
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73. |
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74. |
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75. |
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76. |
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77. |
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78. |
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79. |
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80. |
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81. |
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83. |
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84. |
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85. |
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NCBI article NCBI 1636 |
100. |
OMIM.ORG article Omim 106180 |
101. |
Orphanet article Orphanet ID 117728 |
102. |
Wikipedia article Wikipedia EN (Angiotensin-converting_enzyme) |