This Article Full Text Full Text (PDF) All Versions of this Article: 41/1/25    most recent 01.HYP.0000047465.97065.15v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pereira, A. C. Articles by Krieger, J. E. Search for Related Content PubMed PubMed Citation Articles by Pereira, A. C. Articles by Krieger, J. E. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Related Collections Clinical genetics ACE/Angiotension receptors Genetics of cardiovascular disease

(Hypertension. 2003;41:25.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Angiotensinogen 235T Allele "Dosage" Is Associated With Blood Pressure Phenotypes

Alexandre C. Pereira; Glória F.A. Mota; Roberto S. Cunha; Fernando L. Herbenhoff; José G. Mill; José E. Krieger

From the Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo School of Medicine (A.C.P., G.F.A.M., J.E.K.), São Paulo, Brazil; and the Department of Physiology, Espirito Santo Federal University (R.S.C., F.L.H., J.G.M.), São Paulo, Brazil.

Correspondence to José E. Krieger, MD, PhD, Laboratorio de Genética e Cardiologia Molecular–InCor-Instituto do Coracao–HCFMUSP, Av Dr Eneas de Carvalho Aguiar, 44, 05403-000 Sao Paulo SP, Brazil. E-mail krieger{at}incor.usp.br

The genetic mechanisms underlying interindividual blood pressure variation among humans may reflect, at least in part, clustering of functional gene variants belonging to complex blood pressure control systems. In this study, we investigated the association of specific functional gene variants of the renin-angiotensin system, ACE (I/D) and angiotensinogen (M/T) genes, with blood pressure phenotypes (systolic, mean, diastolic, and pulse pressure), in an ethnically mixed urban population in Brazil. Individuals (n=1421) were randomly selected from the general population of the Vitoria City Metropolitan area. Neither gender, age, smoking status, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, or diabetes was associated with ACE or AGT polymorphism in univariate analysis. No association was found between ACE variants and blood pressure phenotypes. However, a statistically significant association was revealed between the AGT 235T variant and all blood pressure phenotypes, consistent with an additive/codominant mode of action even after adjustment for age and gender (P<0.01). Genotypic analysis contemplating both ACE and AGT variants in the same model did not show any significant interaction between both genetic polymorphisms. In addition, the AGT 235T allele was significantly associated with hypertension in a recessive model, which remained as an independent risk factor for hypertension even after adjustment for age, gender, and ethnicity (OR, 1.33; 95% CI, 1.04 to 1.70). Taken together, these data indicate a linear relation between AGT 235T allele number ("dosage") and blood pressure in an ethnically mixed urban population and confirmed its role as an independent risk factor for hypertension for men and women when in homozygosity.

Key Words: angiotensinogen • angiotensin-converting enzyme • hypertension, genetic • blood pressure • genetics • polymorphism

This article has been cited by other articles:

				Y.-S. Tsai, L. Xu, O. Smithies, and N. Maeda Genetic variations in peroxisome proliferator-activated receptor {gamma} expression affect blood pressure PNAS, November 10, 2009; 106(45): 19084 - 19089. [Abstract] [Full Text] [PDF]

				M. Coylewright, J. F. Reckelhoff, and P. Ouyang Menopause and Hypertension: An Age-Old Debate Hypertension, April 1, 2008; 51(4): 952 - 959. [Full Text] [PDF]

				T. V. Pereira, A. C.F. Nunes, M. Rudnicki, Y. Yamada, A. C. Pereira, and J. E. Krieger Meta-Analysis of the Association of 4 Angiotensinogen Polymorphisms With Essential Hypertension: A Role Beyond M235T? Hypertension, March 1, 2008; 51(3): 778 - 783. [Abstract] [Full Text] [PDF]

				X. Su, L. Lee, X. Li, J. Lv, Y. Hu, S. Zhan, W. Cao, L. Mei, Y.-M. Tang, D. Wang, et al. Association Between Angiotensinogen, Angiotensin II Receptor Genes, and Blood Pressure Response to an Angiotensin-Converting Enzyme Inhibitor Circulation, February 13, 2007; 115(6): 725 - 732. [Abstract] [Full Text] [PDF]

				G. J. J. Silva, E. D. Moreira, A. C. Pereira, J. G. Mill, E. M. Krieger, and J. E. Krieger ACE gene dosage modulates pressure-induced cardiac hypertrophy in mice and men Physiol Genomics, November 21, 2006; 27(3): 237 - 244. [Abstract] [Full Text] [PDF]

				B. C Cholewa and D. L Mattson Influence of elevated renin substrate on angiotensin II and arterial blood pressure in conscious mice Exp Physiol, July 1, 2005; 90(4): 607 - 612. [Abstract] [Full Text] [PDF]

				C. P. R. Klett, D. Anderson, M. Sholook, and J. P. Granger Antisense oligodeoxynucleotides directed against a novel angiotensinogen mRNA-stabilizing protein reduce blood pressure in spontaneously hypertensive rats Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2004; 287(3): R619 - R626. [Abstract] [Full Text] [PDF]

				F. C. Luft Geneticism of Essential Hypertension Hypertension, June 1, 2004; 43(6): 1155 - 1159. [Full Text] [PDF]

				A. C. Pereira, M. S. Floriano, G. F.A. Mota, R. S. Cunha, F. L. Herkenhoff, J. G. Mill, and J. E. Krieger {beta}2 Adrenoceptor Functional Gene Variants, Obesity, and Blood Pressure Level Interactions in the General Population Hypertension, October 1, 2003; 42(4): 685 - 692. [Abstract] [Full Text] [PDF]