(Hypertension. 2000;35:555.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
ß-2 Adrenergic Receptor Gene Variations, Blood Pressure, and Heart Size in Normal Twins
From Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University of Berlin, Germany.
Correspondence to Friedrich C. Luft, Franz Volhard Clinic, Wiltberg Strasse 50, 13122 Berlin, Germany. E-mail luft{at}fvk-berlin.de
Abstract—Genetic variability, which influences cardiovascular phenotypes in normal persons, is likely to be relevant to cardiovascular disease. We studied normal monozygotic and dizygotic twins and found strong genetic influences on blood pressure and heart size. We then relied on the dizygotic twins and their parents to apply molecular genetic techniques. We performed a linkage analysis with markers close to the ß-2 adrenergic receptor (AR) gene locus in the dizygotic twins and their parents and found strong evidence for linkage to the quantitative traits of blood pressure and heart size. We then used allele-specific polymerase chain reaction to genotype the subjects further. We performed an association analysis and found that 4 functionally relevant polymorphisms in the ß-2 AR gene, namely Arg16/Gly, Gln27/Glu, Thr164/Ile, and a variant in the promoter region (-47C/T), were variably associated with blood pressure and heart size differences but were in linkage dysequilibrium with each other. A subsequent conditional analysis suggested that the Arg16/Gly polymorphism exerted the predominant effect. These findings underscore the importance of the ß-2 AR gene to blood pressure regulation, heart size, and probably to the development of hypertension. We suggest that a combined linkage and association approach will elucidate the genetic variability influencing blood pressure and other cardiovascular phenotypes.
Key Words: receptors, adrenergic, beta • genetics • hypertension, genetic • twins • blood pressure
This article has been cited by other articles:
 |
|
 |
|
  J. H. Eisenach, D. R. Schroeder, T. L. Pike, C. P. Johnson, W. G. Schrage, E. M. Snyder, B. D. Johnson, V. D. Garovic, S. T. Turner, and M. J. Joyner Dietary sodium restriction and {beta}2-adrenergic receptor polymorphism modulate cardiovascular function in humans J. Physiol., August 1, 2006; 574(3): 955 - 965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Gu, S. Su, D. Ge, S. Chen, J. Huang, B. Li, R. Chen, and B. Qiang Association Study With 33 Single-Nucleotide Polymorphisms in 11 Candidate Genes for Hypertension in Chinese Hypertension, June 1, 2006; 47(6): 1147 - 1154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Poole, H. Snieder, H. C. Davis, and F. A. Treiber Anger suppression and adiposity modulate association between ADRB2 haplotype and cardiovascular stress reactivity. Psychosom Med, March 1, 2006; 68(2): 207 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Kirstein and P. A. Insel Autonomic Nervous System Pharmacogenomics: A Progress Report Pharmacol. Rev., March 1, 2004; 56(1): 31 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Eisenach, A. M. McGuire, R. M. Schwingler, S. T. Turner, and M. J. Joyner The Arg16/Gly {beta}2-adrenergic receptor polymorphism is associated with altered cardiovascular responses to isometric exercise Physiol Genomics, February 13, 2004; 16(3): 323 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W J Yang, J F Huang, C L Yao, Z J Fan, D L Ge, W Q Gan, G Y Huang, R T Hui, Y Shen, B Q Qiang, et al. Evidence for linkage and association of the markers near the LPL gene with hypertension in Chinese families J. Med. Genet., May 1, 2003; 40(5): e57 - 57. [Full Text] [PDF]
|
|
|
|
|
|
M. Castellano, F. Rossi, M. Giacche, C. Perani, F. Rivadossi, M. L. Muiesan, M. Salvetti, M. Beschi, D. Rizzoni, and E. Agabiti-Rosei {beta}2-Adrenergic Receptor Gene Polymorphism, Age, and Cardiovascular Phenotypes Hypertension, February 1, 2003; 41(2): 361 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tomaszewski, N. J.R. Brain, F. J. Charchar, W. Y.S. Wang, B. Lacka, S. Padmanabahn, J. S. Clark, N. H. Anderson, H. V. Edwards, E. Zukowska-Szczechowska, et al. Essential Hypertension and {beta}2-Adrenergic Receptor Gene: Linkage and Association Analysis Hypertension, September 1, 2002; 40(3): 286 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zaugg, M. C. Schaub, T. Pasch, and D. R. Spahn Modulation of {beta}-adrenergic receptor subtype activities in perioperative medicine: mechanisms and sites of action Br. J. Anaesth., January 1, 2002; 88(1): 101 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tank, A. Diedrich, C. Schroeder, M. Stoffels, G. Franke, A. M. Sharma, F. C. Luft, and J. Jordan Limited Effect of Systemic {beta}-Blockade on Sympathetic Outflow Hypertension, December 1, 2001; 38(6): 1377 - 1381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Bengtsson, M. Orho-Melander, O. Melander, U. Lindblad, J. Ranstam, L. Rastam, and L. Groop {beta}2-Adrenergic Receptor Gene Variation and Hypertension in Subjects With Type 2 Diabetes Hypertension, May 1, 2001; 37(5): 1303 - 1308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kato, T. Sugiyama, H. Morita, H. Kurihara, T. Sato, Y. Yamori, and Y. Yazaki Association Analysis of {beta}2-Adrenergic Receptor Polymorphisms With Hypertension in Japanese Hypertension, February 1, 2001; 37(2): 286 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. C. Luft Twins in Cardiovascular Genetic Research Hypertension, February 1, 2001; 37(2): 350 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sauer, D. Lechner, K. Berlin, C. Plancon, A. Heuermann, H. Lehrach, and I. G. Gut Full flexibility genotyping of single nucleotide polymorphisms by the GOOD assay Nucleic Acids Res., December 1, 2000; 28(23): e100 - e100. [Abstract] [Full Text] [PDF]
|
|