From Cardiovascular Genetics, University of Utah School of Medicine, Salt
Lake City (S.C.H., R.R.W.); the Division of Preventive Medicine, Brigham and
Women's Hospital and Harvard Medical School, Boston, Mass (N.R.C.,
C.H.H.); the Division of Preventive Medicine, University of Alabama at
Birmingham (A.O.); the Division of Epidemiology and Clinical Applications,
National Heart, Lung, and Blood Institute, Bethesda, Md (J.A.C., P.S.A.); the
Department of Medicine, Johns Hopkins University School of Medicine,
Baltimore, Md (W.G.W.); and the School of Public Health and Tropical Medicine,
Tulane University, New Orleans, La (P.K.W.).
Correspondence to Steven C. Hunt, PhD, Cardiovascular Genetics, University of Utah School of Medicine, 410 Chipeta Way, Room 167, Salt Lake City, UT 84108. E-mail steve{at}ucvg.med.utah.edu
Abstract—The
angiotensinogen gene has been linked to essential
hypertension and increased blood pressure. A functional variant
believed to be responsible for hypertension susceptibility occurs at
position -6 in the promoter region of the gene in which an A for G
base pair substitution is associated with higher
angiotensinogen levels. To test whether an allele
within the angiotensinogen gene is related to subsequent
incidence of hypertension and blood pressure response to sustained
sodium reduction, 1509 white male and female subjects participating in
phase II of the Trials of Hypertension Prevention were
genotyped at the angiotensinogen locus.
Participants had diastolic blood pressures between 83 and
89 mm Hg and were randomized in a 2x2 factorial design to sodium
reduction, weight loss, combined intervention, or usual care groups.
Persons in the usual care group with the AA genotype at
nucleotide position -6 had a higher 3-year incidence rate
of hypertension (44.6%) compared with those with the GG
genotype (31.5%), with a relative risk of 1.4 (95% confidence
interval [0.87, 2.34], test for trend across all 3 genotypes,
P=0.10). In contrast, the incidence of hypertension was
significantly lower after sodium reduction for persons with the AA
genotype (relative risk=0.57 [0.34, 0.98] versus usual care)
but not for persons with the GG genotype (relative risk=1.2
[0.79, 1.81], test for trend P=0.02). Decreases of
diastolic blood pressure at 36 months in the sodium
reduction group versus usual care showed a significant trend across all
3 genotypes (P=0.01), with greater net blood
pressure reduction in those with the AA genotype (-2.2
mm Hg) than those with the GG genotype (+1.1 mm Hg). A
similar trend across the 3 genotypes for net systolic
blood pressure reduction (-2.7 for AA versus -0.2 mm Hg for GG)
was not significant (P=0.17). Trends across
genotypes for the effects of weight loss on hypertension
incidence and decreases in blood pressure were similar to those for
sodium reduction. We conclude that the angiotensinogen
genotype may affect blood pressure response to sodium or weight
reduction and the development of hypertension.
© 1998 American Heart Association, Inc.
Scientific Contributions
Angiotensinogen Genotype, Sodium Reduction, Weight Loss, and Prevention of Hypertension
Trials of Hypertension Prevention, Phase II
Key Words: blood pressure • clinical trials • genetics • interaction • prospective study • renin
This article has been cited by other articles:
 |
|
 |
|
  P. R Conlin Genes and environment in blood pressure control--salt intake again shows its importance Am. J. Clinical Nutrition, August 1, 2008; 88(2): 255 - 256. [Full Text] [PDF]
|
|
|
|
|
|
T. Norat, R. Bowman, R. Luben, A. Welch, K. T. Khaw, N. Wareham, and S. Bingham Blood pressure and interactions between the angiotensin polymorphism AGT M235T and sodium intake: a cross-sectional population study Am. J. Clinical Nutrition, August 1, 2008; 88(2): 392 - 397. [Abstract] [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]
|
|
|
|
 |
|
 D. K. Arnett, A. E. Baird, R. A. Barkley, C. T. Basson, E. Boerwinkle, S. K. Ganesh, D. M. Herrington, Y. Hong, C. Jaquish, D. A. McDermott, et al. Relevance of Genetics and Genomics for Prevention and Treatment of Cardiovascular Disease: A Scientific Statement From the American Heart Association Council on Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and Translational Biology Interdisciplinary Working Group Circulation, June 5, 2007; 115(22): 2878 - 2901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Hunt, Y. Xin, L. L. Wu, R. M. Cawthon, H. Coon, S. J. Hasstedt, and P. N. Hopkins Sodium Bicarbonate Cotransporter Polymorphisms Are Associated With Baseline and 10-Year Follow-Up Blood Pressures Hypertension, March 1, 2006; 47(3): 532 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Appel, M. W. Brands, S. R. Daniels, N. Karanja, P. J. Elmer, and F. M. Sacks Dietary Approaches to Prevent and Treat Hypertension: A Scientific Statement From the American Heart Association Hypertension, February 1, 2006; 47(2): 296 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Meneton, X. Jeunemaitre, H. E. de Wardener, and G. A. Macgregor Links Between Dietary Salt Intake, Renal Salt Handling, Blood Pressure, and Cardiovascular Diseases Physiol Rev, April 1, 2005; 85(2): 679 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Engeli, J. Bohnke, K. Gorzelniak, J. Janke, P. Schling, M. Bader, F. C. Luft, and A. M. Sharma Weight Loss and the Renin-Angiotensin-Aldosterone System Hypertension, March 1, 2005; 45(3): 356 - 362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Smith Jr, R. V. Milani, D. K. Arnett, J. R. Crouse III, M. M. McDermott, P. M Ridker, R. S. Rosenson, K. A. Taubert, and P. W.F. Wilson Atherosclerotic Vascular Disease Conference: Writing Group II: Risk Factors Circulation, June 1, 2004; 109(21): 2613 - 2616. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Manunta and G. Bianchi Low-Salt Diet and Diuretic Effect on Blood Pressure and Organ Damage J. Am. Soc. Nephrol., January 1, 2004; 15(90010): S43 - 46. [Abstract] [Full Text]
|
|
|
|
|
|
C. Barlassina, C. Lanzani, P. Manunta, and G. Bianchi Genetics of Essential Hypertension: From Families to Genes J. Am. Soc. Nephrol., November 1, 2002; 13(90003): S155 - 164. [Abstract] [Full Text]
|
|
|
|
|
|
T. A. Kotchen, U. Broeckel, C. E. Grim, P. Hamet, H. Jacob, M. L. Kaldunski, J. M. Kotchen, N. J. Schork, P. J. Tonellato, and A. W. Cowley Jr Identification of Hypertension-Related QTLs in African American Sib Pairs Hypertension, November 1, 2002; 40(5): 634 - 639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. He and P. K Whelton Commentary: Salt intake, hypertension and risk of cardiovascular disease: an important public health challenge Int. J. Epidemiol., April 1, 2002; 31(2): 327 - 331. [Full Text] [PDF]
|
|
|
|
|
|
K. F. Hilgers, C. Delles, R. Veelken, and R. E. Schmieder Angiotensinogen Gene Core Promoter Variants and Non-Modulating Hypertension Hypertension, December 1, 2001; 38(6): 1250 - 1254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Higgins Patients, families and populations at high risk for coronary heart disease Eur. Heart J., September 2, 2001; 22(18): 1682 - 1690. [PDF]
|
|
|
|
 |
|
 A. M Sharma and S. Engeli The renin-angiotensin system in obesity hypertension Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1_suppl): S114 - S119. [PDF]
|
|
|
|
 |
|
 R. M. Krauss, R. H. Eckel, B. Howard, L. J. Appel, S. R. Daniels, R. J. Deckelbaum, J. W. Erdman Jr, P. Kris-Etherton, I. J. Goldberg, T. A. Kotchen, et al. AHA Scientific Statement: AHA Dietary Guidelines: Revision 2000: A Statement for Healthcare Professionals From the Nutrition Committee of the American Heart Association J. Nutr., January 1, 2001; 131(1): 132 - 146. [Full Text]
|
|
|
|
 |
|
 R. M. Krauss, R. H. Eckel, B. Howard, L. J. Appel, S. R. Daniels, R. J. Deckelbaum, J. W. Erdman Jr, P. Kris-Etherton, I. J. Goldberg, T. A. Kotchen, et al. AHA Dietary Guidelines : Revision 2000: A Statement for Healthcare Professionals From the Nutrition Committee of the American Heart Association Stroke, November 1, 2000; 31(11): 2751 - 2766. [Full Text] [PDF]
|
|
|
|
|
|
R. M. Krauss, R. H. Eckel, B. Howard, L. J. Appel, S. R. Daniels, R. J. Deckelbaum, J. W. Erdman Jr, P. Kris-Etherton, I. J. Goldberg, T. A. Kotchen, et al. AHA Dietary Guidelines : Revision 2000: A Statement for Healthcare Professionals From the Nutrition Committee of the American Heart Association Circulation, October 31, 2000; 102(18): 2284 - 2299. [Full Text] [PDF]
|
|
|
|
|
|
N. M Kaplan The dietary guideline for sodium: should we shake it up? No Am. J. Clinical Nutrition, May 1, 2000; 71(5): 1020 - 1026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Fardella, P. Zamorano, L. Mosso, L. Gomez, M. Pinto, J. Soto, E. Oestreicher, P. Cortes, X. Claverie, and J. Montero A-6G Variant of Angiotensinogen Gene and Aldosterone Levels in Hypertensives Hypertension, October 1, 1999; 34(4): 779 - 781. [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]
|
|
|
|
 |
|
 T. A. Kotchen To salt, or not to salt? Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1807 - H1808. [Full Text] [PDF]
|
|
|
|
|
|
T. A. Kotchen Editorial Commentary: Angiotensinogen Genotype and Blood Pressure Responses to Reduced Dietary NaCl and to Weight Loss Hypertension, September 1, 1998; 32(3): 402 - 403. [Full Text] [PDF]
|
|