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The role of β2-adrenergic receptor variation in human hypertension

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Abstract

Hypertension results from a complex and diverse array of metabolic and physiologic processes that interact with environmental factors to ultimately determine blood pressure levels and disease. Consequently, the identification of genes related to hypertension is complicated by the heterogeneity of its etiology and the likelihood that several genes with moderate effects, possibly acting in a contextdependent manner, influence blood pressure and the occurrence of hypertension. A number of studies have recently implicated variation within the b2-adrenergic receptor in blood pressure regulation and the development of hypertension. The role of these findings is reviewed here, and their possible clinical implications in human hypertension.

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References and Recommended Reading

  1. Williams R, Hunt S, Hopkins P, et al.: Genetic basis of familial dyslipidemia and hypertension: 15-year results from Utah. Am J Hypertens 1993, 6:319S-327S.

    PubMed  CAS  Google Scholar 

  2. Rice T, Vogler G, Perusse L, et al.: Cardiovascular risk factors in a French Canadian population: resolution of genetic and familial environmental effects on blood pressure using twins, adoptees, and extensive information on environmental correlates. Genet Epidemiol 1989, 6:571–588.

    Article  PubMed  CAS  Google Scholar 

  3. Perusse L, Rice T, Bouchard C, et al.: Cardiovascular risk factors in a French-Canadian population: resolution of genetic and familial environmental effects on blood pressure by using extensive information on environmental correlates. Am J Hum Genet 1989, 45:240–251.

    PubMed  CAS  Google Scholar 

  4. Schwinn D, Caron M, Lefkowitz R: The beta-adrenergic receptor as a model for molecular structure-function relationships in G-protein-coupled receptors. In The Heart and Cardiovascular System, edn. 2. Edited by Fozzard H, Habes E, Jennings R, Katz A, Morgan H. New York: Raven Press; 1992:1657–1684.

    Google Scholar 

  5. Dzimiri N: Regulation of b-adrenoceptor signaling in cardiac function and disease. Pharmacol Rev 1999, 51:465–501.

    PubMed  CAS  Google Scholar 

  6. DiBona G: Sympathetic nervous system influences on the kidney: role in hypertension. Am J Hypertens 1989, 2:119s-124s.

    PubMed  CAS  Google Scholar 

  7. Schluter K, Zhou X, Piper H: Induction of hypertrophic responsiveness to isoprenaline by TGF-beta in adult rat cardiomyocytes. Am J Physiol 1995, 269:C1311-C1316.

    PubMed  CAS  Google Scholar 

  8. Emorine L, Marullo S, Delavier-Klutchko C, et al.: Structure of the gene for human beta 2-adrenergic receptor: expression and promoter characterization. Proc Natl Acad Sci USA 1987, 84:6995–6999.

    Article  PubMed  CAS  Google Scholar 

  9. Kobilka B, Dixon R, Frielle T, et al.: cDNA for the human β2-adrenergic receptor: a protein with multiple membrane spanning domains and encoded by a gene whose location is shared with that of the receptor for platelet derived growth factor. Proc Natl Acad Sci USA 1987, 84:46–50.

    Article  PubMed  CAS  Google Scholar 

  10. Reihsaus E, Innis M, MacIntyre N, Liggett S: Mutations in the gene encoding for the β 2-adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Biol 1993, 8:334–339.

    PubMed  CAS  Google Scholar 

  11. Yamada K, Ishiyama-Shigemoto S, Ichikawa F, et al.: Polymorphism in the 5-leader cistron of the beta2-adrenergic receptor gene associated with obesity and type 2 diabetes. J Clin Endocrinol Metab 1999, 84:1754–1757.

    Article  PubMed  CAS  Google Scholar 

  12. Green S, Turki J, Innis M, Liggett S: Amino-terminal polymorphisms of the human β 2-adrenergic receptor impart distinct agonist-promoted regulatory properties Biochem 1994, 33:9414–9419. Describes the functional consequences of the Arg16Gly and Gln27Glu polymorphisms after transfection into Chinese hamster fibroblasts. The Gly16 allele showed increased downregulation in response to isoproterenol treatment.

    Article  CAS  Google Scholar 

  13. Green S, Cole G, Jacinto M, et al.: A polymorphism of the human beta 2-adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor. J Biol Chem 1993, 268:23116–23121.

    PubMed  CAS  Google Scholar 

  14. Turki J, Lorenz J, Green S, et al.: Myocardial signaling defects and impaired cardiac function of a human β 2-adrenergic receptor polymorphism expressed in transgenic mice. Proc Natl Acad Sci USA 1996, 93:10483–10488.

    Article  PubMed  CAS  Google Scholar 

  15. Turki J, Pak H, Green S, et al.: Polymorphisms of the β 2 adrenergic receptor in nocturnal and non-nocturnal asthma: evidence that Gly 16 correlates with the nocturnal phenotype. J Clin Invest 1995, 95:1635–1641.

    PubMed  CAS  Google Scholar 

  16. Martinez F, Graves P, Baldini M, et al.: Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing. J Clin Invest 1997, 100:3184–3188.

    PubMed  CAS  Google Scholar 

  17. Hall I, Wheatley A, Wilding P, Liggett S: Association of the Glu27 β 2-adrenoceptor polymorphism with lower airway reactivity in asthmatic subjects. Lancet 1995, 345:1213–1214.

    Article  PubMed  CAS  Google Scholar 

  18. Svetkey L, Timmons P, Emovon O, et al.: Association of hypertension with β2- and α2c10-adrenergic receptor genotype Hypertension 1996, 27:1210–1215.

    PubMed  CAS  Google Scholar 

  19. Svetkey L, Chen YT, McKeown S, et al.: Preliminary evidence of linkage of salt sensitivity in black Americans at the b2-adrenergic receptor locus. Hypertension 1997, 29:918–922.

    PubMed  CAS  Google Scholar 

  20. Kotanko P, Binder A, Tasker J, et al.: Essential hypertension in African Caribbeans associates with a variant of the beta2-adrenoceptor. Hypertension 1997, 30:773–776.

    PubMed  CAS  Google Scholar 

  21. Lang C, Stein M, Brown R, et al.: Attenuation of isoproterenolmediated vasodilatation in blacks. N Engl J Med 1995, 333:155–160.

    Article  PubMed  CAS  Google Scholar 

  22. Gratze G, Fortin J, Labugger R, et al.: β -2 Adrenergic receptor variant affect resting blood pressure and agonist-induced vasodilation in young adult caucasians. Hypertension 1999, 33:1425–1430. Reported in vivo hemodynamic effects of the Arg16Gly polymorphism, including differences in resting blood pressure and vasodilatory response to salbutamol.

    PubMed  CAS  Google Scholar 

  23. Timmermann B, Mo R, Luft F, et al.: Beta-2 adrenoceptor genetic variation is associated with genetic predisposition to essential hypertension: the Bergen Blood Pressure Study. Kidney Int 1998, 53:1455–1460.

    Article  PubMed  CAS  Google Scholar 

  24. Krushkal J, Xiong M, Ferrell R, et al.: Linkage and association of adrenergic and dopamine receptor genes in the distal portion of the long arm of chromosome 5 with systolic blood pressure variation. Hum Mol Genet 1998, 7:1379–1383.

    Article  PubMed  CAS  Google Scholar 

  25. Krushkal J, Ferrell R, Mockrin S, et al.: Genome-wide linkage analyses of systolic blood pressure using highly discordant siblings. Circulation 1999, 99:1407–1410.

    PubMed  CAS  Google Scholar 

  26. Bohm M, Flesch M, Schnabel P: Beta-adrenergic signal transduction in the failing and hypertrophied myocardium. J Mol Med 1997, 75:842–848.

    Article  PubMed  CAS  Google Scholar 

  27. Lind L, Andersson PE, Andren B, et al.: Left ventricular hypertrophy is associated with the insulin resistance metabolic syndrome. J Hypertens 1995, 13:433–438.

    PubMed  CAS  Google Scholar 

  28. Liggett S, Wagoner L, Craft L, et al.: The Ile164 beta2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure. J Clin Invest 1998, 102:1534–1539.

    PubMed  CAS  Google Scholar 

  29. Mori Y, Kim-Motoyama H, Ito Y, et al.: The Gln27Glu beta2-adrenergic receptor variant is associated with obesity due to subcutaneous fat accumulation in Japanese men. Biochem Biophys Res Commun 1999, 258:138–140.

    Article  PubMed  CAS  Google Scholar 

  30. Ishiyama-Shigemoto S, Yamada K, Yuan X, et al.: Association of polymorphisms in the beta2-adrenergic receptor gene with obesity, hypertriglyceridemia, and diabetes mellitus. Diabetologia 1999, 42:98–101.

    Article  PubMed  CAS  Google Scholar 

  31. Meirhaeghe A, Helbecque N, Cottel D, Amouyel P: Beta2-adrenoceptor gene polymorphism, body weight, and physical activity [letter]. Lancet 1999, 353:896.

    Article  PubMed  CAS  Google Scholar 

  32. Hellstrom L, Large V, Reynisdottir S, et al.: The different effects of a Gln27Glu beta 2-adrenoceptor gene polymorphism on obesity in males and in females. J Intern Med 1999, 245:253–259.

    Article  PubMed  CAS  Google Scholar 

  33. Large V, Hellstrom L, Reynisdottir S, et al.: Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function. J Clin Invest 1997, 100:3005–3013. Reported that the Glu27 allele was associated with obesity in females. The Arg16Gly polymorphism, on the other hand, was not associated with obesity but was associated with differences in receptor function in cultured adipocytes.

    PubMed  CAS  Google Scholar 

  34. Lonnqvist F, Wahrenberg H, Hellstrom L, et al.: Lipolytic catecholamine resistance due to decreased beta2-adrenoceptor expression in fat cells. J Clin Invest 1992, 90:2175–2186.

    PubMed  CAS  Google Scholar 

  35. Shek E, Brands M, Hall J: Chronic leptin infusion increases arterial pressure. Hypertension 1998, 31:409–414.

    PubMed  CAS  Google Scholar 

  36. Leyva F, Godsland F, Ghatei M, et al.: Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk. Arterioscler Thromb Vasc Biol 1998, 18:928–933.

    PubMed  CAS  Google Scholar 

  37. Stein C, Nelson R, Deegan R, et al.: Forearm beta adrenergic receptor-mediated vasodilation is impaired, without alteration of forearm norepinephrine spillover, in borderline hypertension. J Clin Invest 1995, 96:579–585.

    Article  PubMed  CAS  Google Scholar 

  38. Chruscinski A, Rohrer D, Schauble E, et al.: Targeted disruption of the b2 adrenergic receptor gene. J Biol Chem 1999, 274:16694–16700. Used gene targeting to inactivate ADRB2 in mice and described the resulting cardiovascular phenotypes, including hypertension during exercise.

    Article  PubMed  CAS  Google Scholar 

  39. Prichard B, Cruickshank J: Beta blockade in hypertension: past, present, and future. In Hypertension: Pathophysiology, Diagnosis, and Management. Edited by Laragh J, Brenner B. New York: Raven Press; 1995:2827–2859.

    Google Scholar 

  40. Liggett S: Polymorphisms of the b2-adrenergic receptor and asthma. Am J Respir Crit Care Med 1997, 156:S156-S162.

    PubMed  CAS  Google Scholar 

  41. Dorn GN, Tepe N, Lorenz J, et al.: Low- and high-level transgenic expression of b2-adrenergic receptors differentially affect cardiac hypertrophy and function in Gaq-overexpressing mice. Proc Natl Acad Sci USA 1999, 96:6400–6405.

    Article  PubMed  CAS  Google Scholar 

  42. Prichard B, Battersby L, Cruickshank J: Overdosage with beta-adrenergic blocking agents. Adverse Drug React Acute Poisoning Rev 1984, 3:91–111.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Human Genetics Center, University of Texas, Houston Health Science Center, PO Box 20337, 77225, Houston, Texas, USA

    Molly S. Bray PhD & Eric Boerwinkle PhD

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  1. Molly S. Bray PhD
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  2. Eric Boerwinkle PhD
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Bray, M.S., Boerwinkle, E. The role of β2-adrenergic receptor variation in human hypertension. Current Science Inc 2, 39–43 (2000). https://doi.org/10.1007/s11906-000-0056-5

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  • DOI: https://doi.org/10.1007/s11906-000-0056-5

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