The AGT gene to be involved in hypertension, hypertensive complications, and diabetic nephropathy is discussed by several publications.
The mutation is very common worldwide. The frequency of the T-allel wird in caucasien is 36%. It seems to exist race differences in allel frequencies and its influence on the development of hypertensive injuries.
The gene AGT is 12kb in size. It consists of 4 exons. Gen locus is on chromosome 1 (1q42-q43).
Hypertension is a very common disease. It is influenced by many genes. The angiontensinogene mutation has a modifying function. It is suggested that hypertensive injuries especially in kidney and heart develop earlier. It is suggestive too that these patients will have a good benefit from ACE-inhibitor therapy.
Angiotensinogen is a peptide hormone. It is secreted as a prohormone and will be activated extracellulary by renin (REN) and angiotensin-converting-enzyme (ACE). These extracallular activators have an important function in regulating the hormone.The renin-agiotensin-system (RAS) playes an important role in boo pressure regulation: Activated angiotensinogen, angiotensin II, is a potent vasoconstrictor and a stimulator of the synthesis of aldosterone. In the kidney microcirculation and glomerular filtrationsrate will be influenced. in clinical studies the influence on the development of hypertensive injuries could be shown.In case of M235T mutation plasma levels of angiotensinogen are elevated. According the enzyme kinetics a higher substrate concentration will result in a higher concentration of product. This way the hypertensive angiotensin II is elevated too. This can explaine the correlation of this mutation to hypertension.
Patients with hypertension with a known family risk for hypertensive injuries.
The importance of the genetic test lays in the estimation of the prognosis an the decision to ACE inhibitor therapy.
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. |
Hegele RA et al. (1994) A polymorphism of the angiotensinogen gene associated with variation in blood pressure in a genetic isolate. |
2. |
Hume GE et al. (2006) Angiotensinogen and transforming growth factor beta1: novel genes in the pathogenesis of Crohn's disease. |
3. |
Frank D et al. (2007) Calsarcin-1 protects against angiotensin-II induced cardiac hypertrophy. |
4. |
Isa MN et al. (1990) Assignment of the human angiotensinogen gene to chromosome 1q42-q43 by nonisotopic in situ hybridization [corrected] |
5. |
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6. |
Gaillard I et al. (1989) Structure of human angiotensinogen gene. |
7. |
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8. |
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9. |
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10. |
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11. |
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12. |
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13. |
Fornage M et al. (1995) Variation at the M235T locus of the angiotensinogen gene and essential hypertension: a population-based case-control study from Rochester, Minnesota. |
14. |
Katsuya T et al. (1995) Association of angiotensinogen gene T235 variant with increased risk of coronary heart disease. |
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Bloem LJ et al. (1995) The serum angiotensinogen concentration and variants of the angiotensinogen gene in white and black children. |
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20. |
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21. |
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22. |
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23. |
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24. |
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25. |
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27. |
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Hillermann R et al. (2005) The Glu298Asp variant of the endothelial nitric oxide synthase gene is associated with an increased risk for abruptio placentae in pre-eclampsia. |
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37. |
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38. |
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39. |
Nakajima T et al. (1999) Functional analysis of a mutation occurring between the two in-frame AUG codons of human angiotensinogen. |
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Guo X et al. (1999) Evidence of a major gene effect for angiotensinogen among Nigerians. |
41. |
Azizi M et al. (2000) Influence of the M235T polymorphism of human angiotensinogen (AGT) on plasma AGT and renin concentrations after ethinylestradiol administration. |
42. |
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52. |
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53. |
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57. |
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58. |
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59. |
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Orphanet article Orphanet ID 119535 |
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