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Gene Review

AGT  -  angiotensinogen (serpin peptidase...

Homo sapiens

Synonyms: ANHU, Angiotensinogen, SERPINA8, Serpin A8
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Disease relevance of AGT


Psychiatry related information on AGT

  • The current results suggested that AGT T235M polymorphism might be a risk factor of vascular dementia [7].
  • We sought to determine whether the M235T angiotensinogen (AGT) polymorphism, either interacting with habitual physical activity (PA) levels or independently, was associated with cardiovascular (CV) hemodynamics during maximal and submaximal exercise [8].
  • The AGT T235 allele does not appear to be a marker for blood pressure variation in this group, but variants on chromosome 1q lying in or near the AGT gene may contribute to individual differences in the blood pressure response to ACE inhibition [9].
  • In this cross-sectional study, we examined the association between functional polymorphisms in the angiotensin converting enzyme (ACE) and angiotensinogen (AGT) genes in 115 bipolar affective disorder (BPAD) patients and 323healthy control subjects [10].
  • The reason of this is not clear, but from the above mentioned seemingly indispensable association of grass-eating with the peroxisomal localization of SPT/AGT it may be related, at least in part, to the food habit of Japanese, especially that of old generation, that they prefer boiled greens rather than frying or raw vegetables [11].

High impact information on AGT

  • The corroboration and replication afforded by these results support the interpretation that molecular variants of AGT constitute inherited predispositions to essential hypertension in humans [12].
  • However, ACE I-D and AGT M235T polymorphisms interacted significantly (P = 0.0166): in subjects with ACE ID and DD genotypes, renal involvement increased from the AGT MM to TT genotypes [13].
  • Our results suggest that polymorphisms at the AGT and ACE gene loci are important markers for predicting progression to chronic renal failure in Caucasian patients with IgA nephropathy [14].
  • Similarly, patients with AGT MT and TT genotypes had higher maximal values of proteinuria than those with the MM genotype (i.e., median values, 2.5 and 3.5 vs. 2.0 g/d, respectively; P < 0.02 by Kruskal-Wallis test) [14].
  • Multivariant analysis, however, detected an interaction between the AGT and ACE gene polymorphisms with the presence of ACE/DD polymorphism adversely affecting disease progression only in patients with the AGT/MM genotype (P = 0.008) [14].

Chemical compound and disease context of AGT


Biological context of AGT

  • Angiotensin II, a potent vasoactive peptide produced by proteolysis of the angiotensinogen (AGT) prohormone, plays a critical role in cardiovascular homeostasis [2].
  • Here, we tested the hypothesis that glial-derived AGT plays an important role in blood pressure regulation in hypertensive mice carrying human renin (hREN) and human AGT transgenes under the control of their own endogenous promoters [20].
  • RESULTS: Of the 12 SNPs genotyped, Glu53Stop in AGT and A>T (-777) in AT1 genes, were monomorphic and not included for further analysis [21].
  • This promoter targets expression of transgene products to astrocytes, the most abundant cell type expressing AGT in brain [22].
  • Because of the inability to dissect the functional role of astrocyte- vs. neuron-derived AGT in vivo by pharmacological approaches, the exact role of neuron-derived AGT in the regulation of blood pressure (BP) and fluid and electrolyte balance remains unclear [23].

Anatomical context of AGT

  • Angiotensinogen (AGT) is mainly expressed in glial cells in close proximity to renin-expressing neurons in the brain [20].
  • The angiotensinogen gene (AGT) is a thrifty gene which increases the risk for common disease with growth of civilization via sodium and body fluid retention [24].
  • In the brain, angiotensinogen (AGT) is expressed in astrocytes and in some neurons important to cardiovascular control, but its functional role remains undefined [22].
  • In one line examined in detail, transgene expression was high in brain and low in tissues outside the central nervous system, and the level of plasma hAGT was not elevated over baseline [22].
  • RESULTS: Human renal proximal tubule epithelial cells bound (125)I-AGT in a time-dependent manner [25].

Associations of AGT with chemical compounds


Physical interactions of AGT

  • Upregulation of human angiotensinogen (AGT) gene transcription by interferon-gamma: Involvement of the STAT1-binding motif in the AGT promoter [28].
  • A substitution (M235T) polymorphism in angiotensinogen (AGT) may interact with ACE I/D polymorphism for the risk of diabetic nephropathy, but their prognostic values have to be established by follow-up studies [29].
  • We show that recombinant glucocorticoid receptor (GR) binds strongly to the AGT gene promoter when nucleoside A is present at -217, and dexamethasone treatment increases the interleukin 6 induced promoter activity of reporter constructs containing nucleoside A at -217 [30].

Enzymatic interactions of AGT

  • Plasma AGT concentration was estimated from plasma angiotensin I which was cleaved by an excess amount of human renin and measured by RIA [31].

Regulatory relationships of AGT

  • IFN gamma treatment up-regulated AGT mRNA level and promoter activity in Hep3B hepatocytes [28].
  • METHODS: Genotyping for the G460W-ADD, M235T-AGT and the insertion/deletion (I/D)-ACE gene polymorphisms was performed in 260 control subjects and 260 ESRD patients using polymerase chain reaction, gel analysis and appropriate restriction digest [32].
  • ACE and AGT genes did not display any difference in clinical or metabolic parameters according to each gene's genotype for either the control or the NIDDM group [33].

Other interactions of AGT


Analytical, diagnostic and therapeutic context of AGT


  1. Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal and overweight subjects. Giacchetti, G., Faloia, E., Mariniello, B., Sardu, C., Gatti, C., Camilloni, M.A., Guerrieri, M., Mantero, F. Am. J. Hypertens. (2002) [Pubmed]
  2. Angiotensinogen gene expression is dependent on signal transducer and activator of transcription 3-mediated p300/cAMP response element binding protein-binding protein coactivator recruitment and histone acetyltransferase activity. Ray, S., Sherman, C.T., Lu, M., Brasier, A.R. Mol. Endocrinol. (2002) [Pubmed]
  3. Influence of the M235T polymorphism of human angiotensinogen (AGT) on plasma AGT and renin concentrations after ethinylestradiol administration. Azizi, M., Hallouin, M.C., Jeunemaitre, X., Guyene, T.T., Ménard, J. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  4. Intragraft messenger RNA expression of angiotensinogen: relationship with transforming growth factor beta-1 and chronic allograft nephropathy in kidney transplant patients. Mas, V., Alvarellos, T., Giraudo, C., Massari, P., De Boccardo, G. Transplantation (2002) [Pubmed]
  5. Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma. Juillerat-Jeanneret, L., Celerier, J., Chapuis Bernasconi, C., Nguyen, G., Wostl, W., Maerki, H.P., Janzer, R.C., Corvol, P., Gasc, J.M. Br. J. Cancer (2004) [Pubmed]
  6. ACE I/D but not AGT (-6)A/G polymorphism is a risk factor for mortality in ARDS. Adamzik, M., Frey, U., Sixt, S., Knemeyer, L., Beiderlinden, M., Peters, J., Siffert, W. Eur. Respir. J. (2007) [Pubmed]
  7. Sequence variants of ACE, AGT, AT1R, and PAI-1 as genetic risk factors for vascular dementia. Kim, Y., Kim, J.H., Nam, Y.J., Kim, Y.J., Yu, K.H., Lee, B.C., Lee, C. Neurosci. Lett. (2006) [Pubmed]
  8. Angiotensinogen M235T polymorphism associates with exercise hemodynamics in postmenopausal women. McCole, S.D., Brown, M.D., Moore, G.E., Ferrell, R.E., Wilund, K.R., Huberty, A., Douglass, L.W., Hagberg, J.M. Physiol. Genomics (2002) [Pubmed]
  9. Renin-angiotensin system gene polymorphisms influence blood pressure and the response to angiotensin converting enzyme inhibition. Hingorani, A.D., Jia, H., Stevens, P.A., Hopper, R., Dickerson, J.E., Brown, M.J. J. Hypertens. (1995) [Pubmed]
  10. Angiotensinogen and angiotensin converting enzyme gene polymorphisms and the risk of bipolar affective disorder in humans. Meira-Lima, I.V., Pereira, A.C., Mota, G.F., Krieger, J.E., Vallada, H. Neurosci. Lett. (2000) [Pubmed]
  11. Primary hyperoxaluria type 1 in Japan. Ichiyama, A., Oda, T., Maeda-Nakai, E. Cell Biochem. Biophys. (2000) [Pubmed]
  12. Molecular basis of human hypertension: role of angiotensinogen. Jeunemaitre, X., Soubrier, F., Kotelevtsev, Y.V., Lifton, R.P., Williams, C.S., Charru, A., Hunt, S.C., Hopkins, P.N., Williams, R.R., Lalouel, J.M. Cell (1992) [Pubmed]
  13. Contribution of genetic polymorphism in the renin-angiotensin system to the development of renal complications in insulin-dependent diabetes: Genetique de la Nephropathie Diabetique (GENEDIAB) study group. Marre, M., Jeunemaitre, X., Gallois, Y., Rodier, M., Chatellier, G., Sert, C., Dusselier, L., Kahal, Z., Chaillous, L., Halimi, S., Muller, A., Sackmann, H., Bauduceau, B., Bled, F., Passa, P., Alhenc-Gelas, F. J. Clin. Invest. (1997) [Pubmed]
  14. Association of angiotensinogen gene T235 variant with progression of immunoglobin A nephropathy in Caucasian patients. Pei, Y., Scholey, J., Thai, K., Suzuki, M., Cattran, D. J. Clin. Invest. (1997) [Pubmed]
  15. Genetic polymorphisms of angiotensin system genes in congenital diaphragmatic hernia associated with persistent pulmonary hypertension. Solari, V., Puri, P. J. Pediatr. Surg. (2004) [Pubmed]
  16. Genetic factors associated with volume-sensitive hypertension. Williams, G.H. Mol. Cell. Endocrinol. (2004) [Pubmed]
  17. T+31C polymorphism (M235T) of the angiotensinogen gene and home blood pressure in the Japanese general population: the Ohasama Study. Matsubara, M., Metoki, H., Katsuya, T., Kikuya, M., Suzuki, M., Michimata, M., Araki, T., Hozawa, A., Tsuji, I., Ogihara, T., Imai, Y. Hypertens. Res. (2003) [Pubmed]
  18. Angiotensin-converting enzyme gene I/D polymorphism in malignant hypertension. Stefansson, B., Ricksten, A., Rymo, L., Aurell, M., Herlitz, H. Blood Press. (2000) [Pubmed]
  19. Mismatch repair mutations override alkyltransferase in conferring resistance to temozolomide but not to 1,3-bis(2-chloroethyl)nitrosourea. Liu, L., Markowitz, S., Gerson, S.L. Cancer Res. (1996) [Pubmed]
  20. Glial-specific ablation of angiotensinogen lowers arterial pressure in renin and angiotensinogen transgenic mice. Sherrod, M., Davis, D.R., Zhou, X., Cassell, M.D., Sigmund, C.D. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2005) [Pubmed]
  21. Chronic renal insufficiency among Asian Indians with type 2 diabetes: I. Role of RAAS gene polymorphisms. Prasad, P., Tiwari, A.K., Kumar, K.M., Ammini, A.C., Gupta, A., Gupta, R., Sharma, A.K., Rao, A.R., Nagendra, R., Chandra, T.S., Tiwari, S.C., Rastogi, P., Gupta, B.L., Thelma, B.K. BMC Med. Genet. (2006) [Pubmed]
  22. Elevated blood pressure in transgenic mice with brain-specific expression of human angiotensinogen driven by the glial fibrillary acidic protein promoter. Morimoto, S., Cassell, M.D., Beltz, T.G., Johnson, A.K., Davisson, R.L., Sigmund, C.D. Circ. Res. (2001) [Pubmed]
  23. Neuron-specific expression of human angiotensinogen in brain causes increased salt appetite. Morimoto, S., Cassell, M.D., Sigmund, C.D. Physiol. Genomics (2002) [Pubmed]
  24. Salt sensitivity of Japanese from the viewpoint of gene polymorphism. Katsuya, T., Ishikawa, K., Sugimoto, K., Rakugi, H., Ogihara, T. Hypertens. Res. (2003) [Pubmed]
  25. Specific receptor for angiotensinogen on human renal cells. Pan, N., Luo, J., Kaiser, S.J., Frome, W.L., Dart, R.A., Tewksbury, D.A. Clin. Chim. Acta (2006) [Pubmed]
  26. Genotype-phenotype relationships for the renin-angiotensin-aldosterone system in a normal population. Paillard, F., Chansel, D., Brand, E., Benetos, A., Thomas, F., Czekalski, S., Ardaillou, R., Soubrier, F. Hypertension (1999) [Pubmed]
  27. Renin angiotensin system gene polymorphisms in pediatric renal transplant recipients. Filler, G., Yang, F., Martin, A., Stolpe, J., Neumayer, H.H., Hocher, B. Pediatric transplantation. (2001) [Pubmed]
  28. Upregulation of human angiotensinogen (AGT) gene transcription by interferon-gamma: Involvement of the STAT1-binding motif in the AGT promoter. Jain, S., Shah, M., Li, Y., Vinukonda, G., Sehgal, P.B., Kumar, A. Biochim. Biophys. Acta (2006) [Pubmed]
  29. Prognostic value of angiotensin-I converting enzyme I/D polymorphism for nephropathy in type 1 diabetes mellitus: a prospective study. Hadjadj, S., Belloum, R., Bouhanick, B., Gallois, Y., Guilloteau, G., Chatellier, G., Alhenc-Gelas, F., Marre, M. J. Am. Soc. Nephrol. (2001) [Pubmed]
  30. A single-nucleotide polymorphism in human angiotensinogen gene is associated with essential hypertension and affects glucocorticoid induced promoter activity. Jain, S., Li, Y., Patil, S., Kumar, A. J. Mol. Med. (2005) [Pubmed]
  31. Nine polymorphisms of angiotensinogen gene in the susceptibility to essential hypertension. Sato, N., Katsuya, T., Nakagawa, T., Ishikawa, K., Fu, Y., Asai, T., Fukuda, M., Suzuki, F., Nakamura, Y., Higaki, J., Ogihara, T. Life Sci. (2000) [Pubmed]
  32. Role of the alpha-adducin genotype on renal disease progression. Nicod, J., Frey, B.M., Frey, F.J., Ferrari, P. Kidney Int. (2002) [Pubmed]
  33. Angiotensin I-converting enzyme and angiotensinogen gene polymorphisms in non-insulin-dependent diabetes mellitus. Lack of relationship with diabetic nephropathy and retinopathy in a Caucasian Mediterranean population. Gutiérrez, C., Vendrell, J., Pastor, R., Llor, C., Aguilar, C., Broch, M., Richart, C. Metab. Clin. Exp. (1997) [Pubmed]
  34. Hypertension genes are genetic markers for insulin sensitivity and resistance. Guo, X., Cheng, S., Taylor, K.D., Cui, J., Hughes, R., Quiñones, M.J., Bulnes-Enriquez, I., De la Rosa, R., Aurea, G., Yang, H., Hsueh, W., Rotter, J.I. Hypertension (2005) [Pubmed]
  35. Angiotensinogen concentrations and renin clearance : implications for blood pressure regulation. Bohlender, J., Ménard, J., Ganten, D., Luft, F.C. Hypertension (2000) [Pubmed]
  36. Renin-angiotensin system gene polymorphisms and premature coronary heart disease. Sekuri, C., Cam, F.S., Ercan, E., Tengiz, I., Sagcan, A., Eser, E., Berdeli, A., Akin, M. Journal of the renin-angiotensin-aldosterone system : JRAAS. (2005) [Pubmed]
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