This Article Full Text 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 Schunkert, H. Articles by Jeunemaitre, X. Search for Related Content PubMed PubMed Citation Articles by Schunkert, H. Articles by Jeunemaitre, X.

(Hypertension. 1997;29:628-633.)
© 1997 American Heart Association, Inc.

Articles

The Angiotensinogen T235 Variant and the Use of Antihypertensive Drugs in a Population-Based Cohort

Heribert Schunkert; Hans-Werner Hense; AnnePaule Gimenez-Roqueplo; Jutta Stieber; Ulrich Keil; Gunter A.J. Riegger; Xavier Jeunemaitre

the Klinik und Poliklinik fur Innere Medizin II, University of Regensburg (H.S., G.A.J.R.); Institut fur Epidemiologie und Sozialmedizin, University of Munster (H.-W.H., U.K.); GSF Forschungszentrum, Institut fur Epidemiologie, Munich-Neuherberg (J.S.) (Germany); and Laboratoire Biologie Moleculaire, Hopital Broussais, and Institut National de la Sante et de la Recherche Medicale (INSERM) Unit 36, College de France, Paris (A.G.-R., X.J.).

Variants of the angiotensinogen gene may increase the risk of developing arterial hypertension, but their effect on the use of antihypertensive medication in the general population remains unclear. Thus, we determined T174M and M235T allele status and angiotensinogen plasma levels in a cross-sectional sample of 634 middle-aged subjects (48.4% men) from the Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Augsburg cohort study. We found no association between T174M allele status and angiotensinogen levels, blood pressure, or use of antihypertensive drugs. In contrast, multivariate analysis revealed that individuals who carried at least one copy of the T235 allele (n=418) had higher systolic and diastolic pressures (P=.007 and .008, respectively) and were more likely to use an antihypertensive drug (1.6-fold risk, P=.04) than homozygotes for the M235 allele (n=216). The likelihood of taking two or more antihypertensive medications was 2.1-fold higher in carriers of the T235 allele (P=.02). Overall, 22.5% of all antihypertensive drugs taken appeared to be attributable to the excess risk associated with this allele. These associations were replicated in two previous surveys carried out on the same individuals over 10 years. Furthermore, the T235 allele was related to higher angiotensinogen plasma levels [15.5±0.31 versus 16.5±0.15 (nmol/L)/L in homozygotes for the M235 and T235 alleles, respectively; P<.01], which were also related to systolic pressure (P=.03) and more intensive antihypertensive medication (P=.03). We conclude that the angiotensinogen T235 allele accounts for a substantial proportion of antihypertensive drug use in this middle-aged, population-based group of white subjects.

Key Words: hypertension, essential • angiotensinogen • genetics • genotype • antihypertensive agents

This article has been cited by other articles:

				M. Nishikino, T. Matsunaga, K. Yasuda, T. Adachi, T. Moritani, G. Tsujimoto, K. Tsuda, and N. Aoki Genetic Variation in the Renin-Angiotensin System and Autonomic Nervous System Function in Young Healthy Japanese Subjects J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4676 - 4681. [Abstract] [Full Text] [PDF]

				J. L. Anderson, J. F. Carlquist, B. D. Home, and J. B. Muhlestein Cardiovascular Pharmacogenomics: Current Status, Future Prospects Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2003; 8(1): 71 - 83. [Abstract] [PDF]

				B. Cvetkovic, H. L. Keen, X. Zhang, D. Davis, B. Yang, and C. D. Sigmund Physiological significance of two common haplotypes of human angiotensinogen using gene targeting in the mouse Physiol Genomics, December 3, 2002; 11(3): 253 - 262. [Abstract] [Full Text] [PDF]

				A. A. Sethi, A. Tybjaerg-Hansen, M.-L. M. Gronholdt, R. Steffensen, P. Schnohr, and B. G. Nordestgaard Angiotensinogen Mutations and Risk for Ischemic Heart Disease, Myocardial Infarction, and Ischemic Cerebrovascular Disease: Six Case-Control Studies from the Copenhagen City Heart Study Ann Intern Med, May 15, 2001; 134(10): 941 - 954. [Abstract] [Full Text] [PDF]

				A. A. Sethi, B. G. Nordestgaard, B. Agerholm-Larsen, E. Frandsen, G. Jensen, and A. Tybjarg-Hansen Angiotensinogen Polymorphisms and Elevated Blood Pressure in the General Population : The Copenhagen City Heart Study Hypertension, March 1, 2001; 37(3): 875 - 881. [Abstract] [Full Text] [PDF]

				G. Emilien, M. Ponchon, C. Caldas, O. Isacson, and J.-M. Maloteaux Impact of genomics on drug discovery and clinical medicine QJM, July 1, 2000; 93(7): 391 - 423. [Abstract] [Full Text] [PDF]

				T. Rankinen, J. Gagnon, L. Perusse, Y. C. Chagnon, T. Rice, A. S. Leon, J. S. Skinner, J. H. Wilmore, D. C. Rao, and C. Bouchard AGT M235T and ACE ID polymorphisms and exercise blood pressure in the HERITAGE Family Study Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H368 - H374. [Abstract] [Full Text] [PDF]

				P. Corvol, A. Persu, A.-P. Gimenez-Roqueplo, and X. Jeunemaitre Seven Lessons From Two Candidate Genes in Human Essential Hypertension : Angiotensinogen and Epithelial Sodium Channel Hypertension, June 1, 1999; 33(6): 1324 - 1331. [Abstract] [Full Text] [PDF]

				H. Schunkert, U. Brockel, C. Hengstenberg, A. Luchner, M. W. Muscholl, K. Kurzidim, B. Kuch, A. Doring, G.u. A. J. Riegger, and H.-W. Hense Familial predisposition of left ventricular hypertrophy J. Am. Coll. Cardiol., May 1, 1999; 33(6): 1685 - 1691. [Abstract] [Full Text] [PDF]

				S. C. Hunt, N. R. Cook, A. Oberman, J. A. Cutler, C. H. Hennekens, P. S. Allender, W. G. Walker, P. K. Whelton, and R. R. Williams Angiotensinogen Genotype, Sodium Reduction, Weight Loss, and Prevention of Hypertension : Trials of Hypertension Prevention, Phase II Hypertension, September 1, 1998; 32(3): 393 - 401. [Abstract] [Full Text] [PDF]

				H. Schunkert, H.-W. Hense, A. Doring, G. A. J. Riegger, and W. Siffert Association Between a Polymorphism in the G Protein ß3 Subunit Gene and Lower Renin and Elevated Diastolic Blood Pressure Levels Hypertension, September 1, 1998; 32(3): 510 - 513. [Abstract] [Full Text] [PDF]

				R. Kunz, R. Kreutz, J. Beige, A. Distler, and A. M. Sharma Association Between the Angiotensinogen 235T-Variant and Essential Hypertension in Whites : A Systematic Review and Methodological Appraisal Hypertension, December 1, 1997; 30(6): 1331 - 1337. [Abstract] [Full Text]

				P. Corvol and X. Jeunemaitre Molecular Genetics of Human Hypertension: Role of Angiotensinogen Endocr. Rev., October 1, 1997; 18(5): 662 - 677. [Abstract] [Full Text]