on July 25, 2005
Published online before print July 25, 2005, doi: 10.1161/01.HYP.0000174988.81829.72
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 24, 2005
From the Study Coordinating Centre, Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, University of Leuven, Belgium (Y.L., L.T., T.K., J.A.S); the Division of Nephrology, Dialysis, and Hypertension, University Vita Salute San Raffaele, Milan, Italy (L.Z., G.B.); and the Department of Pharmacology and Toxicology, Cardiovascular Research Institute, Maastricht University, the Netherlands (H.S.-B.). * To whom correspondence should be addressed. E-mail: jan.staessen{at}med.kuleuven.be.
Abstract--Preliminary evidence from 1 case-control study suggested that in hypertensive patients, the
Revised on April 14, 2005
Cardiovascular Risk in Relation to
Yan Li; 
-Adducin Gly460Trp Polymorphism and Systolic Pressure. A Prospective Population Study
-adducin 460Trp allele might be associated with a 2-fold higher risk of coronary heart disease. In a prospective population study, we investigated whether the -adducin Gly460Trp polymorphism predicted mortality and morbidity. From August 1985 until July 2003, we randomly recruited 2235 Belgian residents. We obtained information on vital status (until July 1, 2004) and the incidence of events via registries and repeat examinations (median 3). In Cox regression, before and after adjustment for other risk factors, we found strong interaction between systolic blood pressure at baseline, analyzed as a continuous variable, and the -adducin polymorphism in relation to total (P=0.01) and cardiovascular mortality (P=0.007) and all cardiovascular (P=0.003), cardiac (P=0.001), and coronary events (P=0.03). The hazard ratio for total mortality associated with the Trp allele relative to GlyGly homozygosity was 2.30 (95% confidence interval, 1.12 to 4.72; P=0.02) in patients with stage-2 systolic hypertension (
160 mm Hg) and 0.88 (0.61 to 1.26; P=0.48) in the other participants. For all cardiovascular complications, these estimates were 2.94 (1.28 to 6.74; P=0.01) and 0.83 (0.58 to 1.20; P=0.32), respectively. For all cardiovascular events, the positive predictive value and the attributable risk associated with the Trp allele in patients with stage-2 systolic hypertension were 76.9% and 44.3%, respectively. In conclusion, the -adducin Gly460Trp polymorphism, in combination with systolic blood pressure, is a strong predictor of cardiovascular mortality and morbidity.
Key words: genes • epidemiology • morbidity
This article has been cited by other articles:
 |
|
 |
|
  T. W. Hansen, L. Thijs, J. Boggia, Y. Li, M. Kikuya, K. Bjorklund-Bodegard, T. Richart, T. Ohkubo, J. Jeppesen, C. Torp-Pedersen, et al. Prognostic Value of Ambulatory Heart Rate Revisited in 6928 Subjects From 6 Populations Hypertension, August 1, 2008; 52(2): 229 - 235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Manunta, G. Lavery, C. Lanzani, P. S. Braund, M. Simonini, C. Bodycote, L. Zagato, S. Delli Carpini, C. Tantardini, E. Brioni, et al. Physiological Interaction Between {alpha}-Adducin and WNK1-NEDD4L Pathways on Sodium-Related Blood Pressure Regulation Hypertension, August 1, 2008; 52(2): 366 - 372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Staessen, T. Kuznetsova, H. Zhang, M. Maillard, M. Bochud, S. Hasenkamp, J. Westerkamp, T. Richart, L. Thijs, X. Li, et al. Blood Pressure and Renal Sodium Handling in Relation to Genetic Variation in the DRD1 Promoter and GRK4 Hypertension, June 1, 2008; 51(6): 1643 - 1650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Zafarmand, Y. T. van der Schouw, D. E. Grobbee, P. W. de Leeuw, and M. L. Bots {alpha}-Adducin Gly460Trp Variant Increases the Risk of Stroke in Hypertensive Dutch Women Hypertension, June 1, 2008; 51(6): 1665 - 1670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cappuzzello, R. Melchionna, A. Mangoni, G. Tripodi, P. Ferrari, L. Torielli, D. Arcelli, M. Helmer-Citterich, G. Bianchi, M. C. Capogrossi, et al. Role of rat {alpha} adducin in angiogenesis: Null effect of the F316Y polymorphism Cardiovasc Res, August 1, 2007; 75(3): 608 - 617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, L. Zagato, T. Kuznetsova, G. Tripodi, G. Zerbini, T. Richart, L. Thijs, P. Manunta, J.-G. Wang, G. Bianchi, et al. Angiotensin-Converting Enzyme I/D and {alpha}-Adducin Gly460Trp Polymorphisms: From Angiotensin-Converting Enzyme Activity to Cardiovascular Outcome Hypertension, June 1, 2007; 49(6): 1291 - 1297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kikuya, T. W. Hansen, L. Thijs, K. Bjorklund-Bodegard, T. Kuznetsova, T. Ohkubo, T. Richart, C. Torp-Pedersen, L. Lind, H. Ibsen, et al. Diagnostic Thresholds for Ambulatory Blood Pressure Monitoring Based on 10-Year Cardiovascular Risk Circulation, April 24, 2007; 115(16): 2145 - 2152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yazdanpanah, F. A. Sayed-Tabatabaei, A. Hofman, Y. S. Aulchenko, B. A. Oostra, B. H.C. Stricker, H. A.P. Pols, S. W.J. Lamberts, J. C.M. Witteman, J. A.M.J.L. Janssen, et al. The {alpha}-Adducin Gene Is Associated With Macrovascular Complications and Mortality in Patients With Type 2 Diabetes. Diabetes, October 1, 2006; 55(10): 2922 - 2927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Manunta and G. Bianchi Pharmacogenomics and Pharmacogenetics of Hypertension: Update and Perspectives--The Adducin Paradigm J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S30 - S35. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bianchi Genetic variations of tubular sodium reabsorption leading to "primary" hypertension: from gene polymorphism to clinical symptoms Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1536 - R1549. [Abstract] [Full Text] [PDF]
|
|