The pharmacogenetics of β-adrenergic receptor antagonists in the treatment of hypertension and heart failure

Expert Opinion on Drug Metabolism and Toxicology

Volumn 8, Issue 7, 2012, Pages 767-790

  Chan, Sze Wa ^a   Hu, Miao ^a   Tomlinson, Brian ^a  

^a CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

Author keywords

adrenergic receptors; blockers; cytochrome P450 2D6; heart failure; hypertension; pharmacogenetics

Indexed keywords

3 ISOPROPYLAMINO 1 (7 METHYL 4 INDANYLOXY) 2 BUTANOL; ACEBUTOLOL; AMIODARONE; ATENOLOL; BETA 1 ADRENERGIC RECEPTOR; BETA ADRENERGIC RECEPTOR STIMULATING AGENT; BETAXOLOL; BISOPROLOL; BUCINDOLOL; CARTEOLOL; CARVEDILOL; CELIPROLOL; CYTOCHROME P450 2D6; DRUG METABOLIZING ENZYME; FLUOXETINE; GLUCURONOSYLTRANSFERASE; LABETALOL; METOPROLOL; NADOLOL; NEBIVOLOL; OXPRENOLOL; PAROXETINE; PENBUTOLOL; PINDOLOL; PROPAFENONE; PROPRANOLOL; SOTALOL; TIMOLOL; UNINDEXED DRUG; VERAPAMIL;

BLOOD PRESSURE; BRADYCARDIA; BRONCHOSPASM; DEPRESSION; DRUG BIOAVAILABILITY; DRUG DOSE TITRATION; DRUG ELIMINATION; DRUG HALF LIFE; DRUG SELECTIVITY; DRUG TARGETING; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENOTYPE; HEART ARRHYTHMIA; HEART FAILURE; HEART LEFT VENTRICLE EJECTION FRACTION; HEART RATE; HUMAN; HYPERTENSION; INTRINSIC SYMPATHOMIMETIC ACTIVITY; ISCHEMIC HEART DISEASE; LIPID SOLUBILITY; META ANALYSIS (TOPIC); NORADRENALIN RELEASE; PHARMACOGENETICS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SINGLE DRUG DOSE; SLEEP DISORDER; VASOCONSTRICTION; VASODILATATION;

ADRENERGIC BETA-ANTAGONISTS; BLOOD PRESSURE; CYTOCHROME P-450 CYP2D6; GENOTYPE; HEART FAILURE; HUMANS; HYPERTENSION; PHARMACOGENETICS; POLYMORPHISM, GENETIC; RECEPTORS, ADRENERGIC, BETA; SIGNAL TRANSDUCTION;

EID: 84862577490     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1517/17425255.2012.685157     Document Type: Review

References (160)

1. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005;366:1545-53 (Pubitemid 41540112)
2. National Institute for Health and Clinical Excellence (NICE). Hypertension (update): full guideline. Available from: http://www.nice.org.uk/ guidance/index.jsp?action= download&o=54727 [Last accessed 6 November 2011]
3. Williams B, Poulter NR, Brown MJ, et al. British hypertension society guidelines for hypertension management 2004 (BHS-IV): summary. BMJ 2004;328:634-40 (Pubitemid 38340037)
4. Williams B, Poulter NR, Brown MJ, et al. Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004-BHS IV. J Hum Hypertens 2004;18:139-85 (Pubitemid 38425770)
5. Tomlinson B, Dalal JJ, Huang J, et al. The role of beta-blockers in the management of hypertension: an Asian perspective. Curr Med Res Opin 2011;27:1021-33
6. Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: is it a wise choice? Lancet 2004;364:1684-9 (Pubitemid 39458144)
7. Aursnes I, Osnes JB, Tvete IF, et al. Does atenolol differ from other beta-adrenergic blockers? BMC Clin Pharmacol 2007;7:4
8. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. Br Med J 2009;338:1245-53
9. Materson BJ. Variability in response to antihypertensive drugs. Am J Med 2007;120:S10-20 (Pubitemid 46497039)
10. Frishman WH, Saunders E. Beta-Adrenergic Blockers. J Clin Hypertens (Greenwich) 2011;13:649-53
11. Richardson DW, Freund J, Gear AS, et al. Effect of propranolol on elevated arterial blood pressure. Circulation 1968;37:534-42
12. Materson BJ, Reda DJ, Cushman WC. Department of veterans Affairs single-drug therapy of hypertension study. Revised figures and new data. department of veterans affairs cooperative study group on antihypertensive agents. Am J Hypertens 1995;8:189-92
13. Kurnik D, Li C, Sofowora GG, et al. Beta-1-adrenoceptor genetic variants and ethnicity independently affect response to beta-blockade. Pharmacogenet Genomics 2008;18:895-902
14. Prisant LM, Mensah GA. Use of beta-adrenergic receptor blockers in blacks. J Clin Pharmacol 1996;36:867-73 (Pubitemid 26384475)
15. Yancy CW, Fowler MB, Colucci WS, et al. Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure. N Engl J Med 2001;344:1358-65 (Pubitemid 32378390)
16. Sagnella GA. Why is plasma renin activity lower in populations of African origin? J Hum Hypertens 2001;15:17-25 (Pubitemid 32106764)
17. Joubert PH, Venter CP, Wellstein A. Ethnic differences in response to beta-blockade: fact or artefact? A study with bisoprolol and propranolol. Eur J Clin Pharmacol 1988;34:363-8
18. Zhou HH, Koshakji RP, Silberstein DJ, et al. Altered sensitivity to and clearance of propranolol in men of Chinese descent as compared with American whites. N Engl J Med 1989;320:565-70 The first study to show the difference in response to propranolol between Chinese and white subjects. (Pubitemid 19070541)
19. Zhou HH, Wood AJ. Increased suppression of exercise-induced increase in renin by propranolol in Chinese subjects. Clin Pharmacol Ther 1991;50:150-6
20. Zhou HH, Wood AJ. Differences in stereoselective disposition of propranolol do not explain sensitivity differences between white and Chinese subjects: correlation between the clearance of (-)- and (+)-propranolol. Clin Pharmacol Ther 1990;47:719-23 (Pubitemid 20207329)
21. Zhou HH, Shay SD, Wood AJ. Contribution of differences in plasma binding of propranolol to ethnic differences in sensitivity. Comparison between Chinese and Caucasians. Chin Med J (Engl) 1993;106:898-902 This study showed the difference in protein binding of propranolol between Chinese and Caucasians. (Pubitemid 24049142)
22. Lai ML, Wang SL, Lai MD, et al. Propranolol disposition in Chinese subjects of different CYP2D6 genotypes. Clin Pharmacol Ther 1995;58:264-8
23. Huang CW, Lai ML, Lin MS, et al. Dose-response relationships of propranolol in Chinese subjects with different CYP2D6 genotypes. J Chin Med Assoc 2003;66:57-62
24. Seedat YK, Stewart-Wynne EG, Reddy J, et al. Experiences with beta-adrenergic blockade drugs in hypertension. S Afr Med J 1973;47:259-62
25. Bristow MR, Ginsburg R, Minobe W, et al. Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. N Engl J Med 1982;307:205-11 (Pubitemid 12079105)
26. Brodde OE. Beta-adrenoceptors in cardiac disease. Pharmacol Ther 1993;60:405-30
27. Gauthier C, Leblais V, Kobzik L, et al. The negative inotropic effect of beta3-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle. J Clin Invest 1998;102:1377-84 (Pubitemid 28467566)
28. Small KM, Wagoner LE, Levin AM, et al. Synergistic polymorphisms of beta1- and alpha2C-adrenergic receptors and the risk of congestive heart failure. N Engl J Med 2002;347:1135-42
29. Dorn GW II. Adrenergic signaling polymorphisms and their impact on cardiovascular disease. Physiol Rev 2010;90:1013-62 Detailed review of polymorphisms in the adrenergic pathways and their consequences.
30. Cruikshank JM, McAinsh J. Beta blockers and quality of life. Br J Clin Pract 1992;46:34-8
31. Cheymol G, Poirier JM, Carrupt PA, et al. Pharmacokinetics of beta-adrenoceptor blockers in obese and normal volunteers. Br J Clin Pharmacol 1997;43:563-70 (Pubitemid 27283564)
32. Cruickshank JM. Are we misunderstanding beta-blockers. Int J Cardiol 2007;120:10-27 (Pubitemid 47008996)
33. Prisant LM. Nebivolol: pharmacologic profile of an ultraselective, vasodilatory beta(1)-blocker. J Clin Pharmacol 2008;48:225-39
34. Wellstein A, Palm D, Belz GG. Affinity and selectivity of beta-adrenoceptor antagonists in vitro. J Cardiovasc Pharmacol 1986;8(Suppl 11):S36-40 (Pubitemid 17086482)
35. Sarafidis PA, Bakris GL. Antihypertensive therapy and the risk of new-onset diabetes. Diabetes Care 2006;29:1167-9 (Pubitemid 44115265)
36. Bristow MR. Treatment of chronic heart failure with beta-adrenergic receptor antagonists: a convergence of receptor pharmacology and clinical cardiology. Circ Res 2011;109:1176-94 This paper reviews the development of the use of β-blockers in heart failure and some of the relevant pharmacogenetics.
37. Smart NA, Kwok N, Holland DJ, et al. Bucindolol: a pharmacogenomic perspective on its use in chronic heart failure. Clin Med Insights Cardiol 2011;5:55-66
38. DeQuattro V, Li D. Sympatholytic therapy in primary hypertension: a user friendly role for the future. J Hum Hypertens 2002;16(Suppl 1):S118-23 (Pubitemid 34441147)
39. Frishman WH. Drug therapy. Pindolol: a new beta-adrenoceptor antagonist with partial agonist activity. N Engl J Med 1983;308:940-4 (Pubitemid 13110427)
40. Baker JG, Hill SJ, Summers RJ. Evolution of beta-blockers: from anti-anginal drugs to ligand-directed signalling. Trends Pharmacol Sci 2011;32:227-34 Recent review of interactions of β-blockers with the receptors.
41. Kaye DM, Smirk B, Williams C, et al. Beta-adrenoceptor genotype influences the response to carvedilol in patients with congestive heart failure. Pharmacogenetics 2003;13:379-82 (Pubitemid 36900732)
42. Man in't Veld AJ, Van den Meiracker AH, Schalekamp MA. Do beta-blockers really increase peripheral vascular resistance? Review of the literature and new observations under basal conditions. Am J Hypertens 1988;1:91-6
43. Prichard BN, Tomlinson B, Walden RJ, et al. The beta-adrenergic blockade withdrawal phenomenon. J Cardiovasc Pharmacol 1983;5:S56-62
44. Walden RJ, Tomlinson B, Graham B, et al. Withdrawal phenomena after atenolol and bopindolol: haemodynamic responses in healthy volunteers. Br J Clin Pharmacol 1990;30:557-65 (Pubitemid 20346481)
45. Reiter MJ. Cardiovascular drug class specificity: beta-blockers. Prog Cardiovasc Dis 2004;47:11-33 (Pubitemid 39420270)
46. Frazier EP, Michel-Reher MB, van Loenen P, et al. Lack of evidence that nebivolol is a beta-adrenoceptor agonist. Eur J Pharmacol 2011;654:86-91
47. Rozec B, Erfanian M, Laurent K, et al. Nebivolol, a vasodilating selective beta (1)-blocker, is a beta(3)-adrenoceptor agonist in the nonfailing transplanted human heart. J Am Coll Cardiol 2009;53:1532-8
48. El Desoky ES, Derendorf H, Klotz U. Variability in response to cardiovascular drugs. Curr Clin Pharmacol 2006;1:35-46
49. Zanger UM, Raimundo S, Eichelbaum M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch Pharmacol 2004;369:23-37 (Pubitemid 38161221)
50. Aronow WS, Fleg JL, Pepine CJ, et al. ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of cardiology foundation task force on clinical expert consensus documents. Circulation 2011;123:2434-506
51. Brodde OE, Kroemer HK. Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung 2003;53:814-22
52. Takekuma Y, Takenaka T, Kiyokawa M, et al. Contribution of polymorphisms in UDP-glucuronosyltransferase and CYP2D6 to the individual variation in disposition of carvedilol. J Pharm Pharm Sci 2006;9:101-12 (Pubitemid 43338063)
53. Takekuma Y, Takenaka T, Yamazaki K, et al. Stereoselective metabolism of racemic carvedilol by UGT1A1 and UGT2B7, and effects of mutation of these enzymes on glucuronidation activity. Biol Pharm Bull 2007;30:2146-53 (Pubitemid 350097059)
54. Anderson JR, Nawarskas JJ. Cardiovascular drug-drug interactions. Cardiol Clin 2001;19:215-34,v
55. Kato Y, Miyazaki T, Kano T, et al. Involvement of influx and efflux transport systems in gastrointestinal absorption of celiprolol. J Pharm Sci 2009;98:2529-39
56. Ieiri I, Doi Y, Maeda K, et al. Microdosing clinical study: pharmacokinetic, pharmacogenomic (SLCO2B1), and interaction (grapefruit juice) profiles of celiprolol following the oral microdose and therapeutic dose. J Clin Pharmacol 2011; Published online May 18, 2011
57. Schafer-Korting M, Kirch W, Axthelm T, et al. Atenolol interaction with aspirin, allopurinol, and ampicillin. Clin Pharmacol Ther 1983;33:283-8 (Pubitemid 13089516)
58. Ward SA, Walle T, Walle UK, et al. Propranolol metabolism is determined by both mephenytoin and debrisoquin hydroxylase-activities. Clin Pharmacol Ther 1989;45:72-9 (Pubitemid 19047149)
59. Hu M, Mak VWL, Chu TTY, et al. Pharmacogenetics of HMG-CoA reductase inhibitors: optimizing the prevention of coronary heart disease. Curr Pharm Pers Med 2009;7:1-26
60. Lennard MS, Jackson PR, Freestone S, et al. The relationship between debrisoquine oxidation phenotype and the pharmacokinetics and pharmacodynamics of propranolol. Br J Clin Pharmacol 1984;17:679-85 (Pubitemid 14068500)
61. Johnson JA, Burlew BS. Metoprolol metabolism via cytochrome P4502D6 in ethnic populations. Drug Metab Dispos 1996;24:350-5 (Pubitemid 26087089)
62. Ismail R, Teh LK. The relevance of CYP2D6 genetic polymorphism on chronic metoprolol therapy in cardiovascular patients. J Clin Pharm Ther 2006;31:99-109
63. Lefebvre J, Poirier L, Poirier P, et al. The influence of CYP2D6 phenotype on the clinical response of nebivolol in patients with essential hypertension. Br J Clin Pharmacol 2007;63:575-82 (Pubitemid 46632567)
64. Fux R, Morike K, Prohmer AM, et al. Impact of CYP2D6 genotype on adverse effects during treatment with metoprolol: a prospective clinical study. Clin Pharmacol Ther 2005;78:378-87 (Pubitemid 41393673)
65. Rau T, Heide R, Bergmann K, et al. Effect of the CYP2D6 genotype on metoprolol metabolism persists during long-term treatment. Pharmacogenetics 2002;12:465-72 (Pubitemid 34913529)
66. Huang J, Chuang SK, Cheng CL, et al. Pharmacokinetics of metoprolol enantiomers in Chinese subjects of major CYP2D6 genotypes. Clin Pharmacol Ther 1999;65:402-7 (Pubitemid 29196543)
67. Bijl MJ, Visser LE, van Schaik RH, et al. Genetic variation in the CYP2D6 gene is associated with a lower heart rate and blood pressure in beta-blocker users. Clin Pharmacol Ther 2009;85:45-50 A large study of the effects of the CYP2D6 polymorphisms in β-blocker users.
68. Rau T, Wuttke H, Michels LM, et al. Impact of the CYP2D6 genotype on the clinical effects of metoprolol: a prospective longitudinal study. Clin Pharmacol Ther 2009;85:269-72
69. Yuan H, Huang Z, Yang G, et al. Effects of polymorphism of the beta(1) adrenoreceptor and CYP2D6 on the therapeutic effects of metoprolol. J Int Med Res 2008;36:1354-62
70. Nozawa T, Taguchi M, Tahara K, et al. Influence of CYP2D6 genotype on metoprolol plasma concentration and beta-adrenergic inhibition during long-term treatment: a comparison with bisoprolol. J Cardiovasc Pharmacol 2005;46:713-20 A detailed study of CYP2D6 polymorphisms and effects of two β-blockers.
71. Goryachkina K, Burbello A, Boldueva S, et al. CYP2D6 is a major determinant of metoprolol disposition and effects in hospitalized Russian patients treated for acute myocardial infarction. Eur J Clin Pharmacol 2008;64:1163-73
72. Wuttke H, Rau T, Heide R, et al. Increased frequency of cytochrome P450 2D6 poor metabolizers among patients with metoprolol-associated adverse effects. Clin Pharmacol Ther 2002;72:429-37
73. Swen JJ, Nijenhuis M, de Boer A, et al. Pharmacogenetics: from bench to byte - an update of guidelines. Clin Pharmacol Ther 2011;89:662-73
74. Terra SG, Pauly DF, Lee CR, et al. Beta-Adrenergic receptor polymorphisms and responses during titration of metoprolol controlled release/extended release in heart failure. Clin Pharmacol Ther 2005;77:127-37 (Pubitemid 40269128)
75. Zineh I, Beitelshees AL, Gaedigk A, et al. Pharmacokinetics and CYP2D6 genotypes do not predict metoprolol adverse events or efficacy in hypertension. Clin Pharmacol Ther 2004;76:536-44 (Pubitemid 39601544)
76. Shin J, Johnson JA. Pharmacogenetics of beta-blockers. Pharmacotherapy 2007;27:874-87 A detailed review of β-blocker pharmacogenetics.
77. Zhou HH, Wood AJ. Stereoselective disposition of carvedilol is determined by CYP2D6. Clin Pharmacol Ther 1995;57:518-24
78. Honda M, Nozawa T, Igarashi N, et al. Effect of CYP2D6*10 on the pharmacokinetics of R- and S-carvedilol in healthy Japanese volunteers. Biol Pharm Bull 2005;28:1476-9 (Pubitemid 41379702)
79. Giessmann T, Modess C, Hecker U, et al. CYP2D6 genotype and induction of intestinal drug transporters by rifampin predict presystemic clearance of carvedilol in healthy subjects. Clin Pharmacol Ther 2004;75:213-22 (Pubitemid 38314871)
80. Graff DW, Williamson KM, Pieper JA, et al. Effect of fluoxetine on carvedilol pharmacokinetics, CYP2D6 activity, and autonomic balance in heart failure patients. J Clin Pharmacol 2001;41:97-106
81. Sehrt D, Meineke I, Tzvetkov M, et al. Carvedilol pharmacokinetics and pharmacodynamics in relation to CYP2D6 and ADRB pharmacogenetics. Pharmacogenomics 2011;12:783-95
82. Baudhuin LM, Miller WL, Train L, et al. Relation of ADRB1, CYP2D6, and UGT1A1 polymorphisms with dose of, and response to, carvedilol or metoprolol therapy in patients with chronic heart failure. Am J Cardiol 2010;106:402-8
83. Takekuma Y, Takenaka T, Kiyokawa M, et al. Evaluation of effects of polymorphism for metabolic enzymes on pharmacokinetics of carvedilol by population pharmacokinetic analysis. Biol Pharm Bull 2007;30:537-42 (Pubitemid 46355942)
84. Honda M, Toyoda W, Shimizu T, et al. UGT2B7*3 did not affect the pharmacokinetics of R- and S-carvedilol in healthy Japanese. Drug Metab Pharmacokinet 2007;22:382-6
85. Kirch W, Rose I, Klingmann I, et al. Interaction of bisoprolol with cimetidine and rifampicin. Eur J Clin Pharmacol 1986;31:59-62 (Pubitemid 16017453)
86. Bristow MR, Murphy GA, Krause-Steinrauf H, et al. An alpha2C-adrenergic receptor polymorphism alters the norepinephrine-lowering effects and therapeutic response of the beta-blocker bucindolol in chronic heart failure. Circ Heart Fail 2010;3:21-8
87. Muthumala A, Drenos F, Elliott PM, et al. Role of beta adrenergic receptor polymorphisms in heart failure: systematic review and meta-analysis. Eur J Heart Fail 2008;10:3-13
88. Terra SG, McGorray SP, Wallace MR, et al. Linkage disequilibrium of common beta-1 adrenergic receptor polymorphisms. Clin Pharmacol Ther 2002;71:P70-0
89. Belfer I, Buzas B, Evans C, et al. Haplotype structure of the beta adrenergic receptor genes in US Caucasians and African Americans. Eur J Hum Genet 2005;13:341-51 (Pubitemid 40360790)
90. Mason DA, Moore JD, Green SA, et al. A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor. J Biol Chem 1999;274:12670-4
91. Levin MC, Marullo S, Muntaner O, et al. The myocardium-protective Gly-49 variant of the beta 1-adrenergic receptor exhibits constitutive activity and increased desensitization and down-regulation. J Biol Chem 2002;277:30429-35 (Pubitemid 34970733)
92. Green SA, Turki J, Innis M, et al. Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 1994;33:9414-19 (Pubitemid 24272896)
93. Green SA, 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;268:23116-21 (Pubitemid 23328021)
94. Evans DA, McLeod HL, Pritchard S, et al. Interethnic variability in human drug responses. Drug Metab Dispos 2001;29:606-10 (Pubitemid 32275545)
95. Brodde OE. Beta1- and beta2-adrenoceptor polymorphisms and cardiovascular diseases. Fundam Clin Pharmacol 2008;22:107-25 Review of β-adrenoceptor polymorphisms in cardiovascular diseases.
96. Leineweber K, Heusch G. Beta 1- and beta 2-adrenoceptor polymorphisms and cardiovascular diseases. Br J Pharmacol 2009;158:61-9
97. Hahntow IN, Koopmans RP, Michel MC. The beta2-adrenoceptor gene and hypertension: is it the promoter or the coding region or neither? J Hypertens 2006;24:1003-7 (Pubitemid 43772303)
98. Thomsen M, Dahl M, Tybjaerg-Hansen A, et al. Beta(2)-adrenergic receptor Thr164IIe polymorphism, blood pressure and ischaemic heart disease in 66 750 individuals. J Intern Med 2012;271:305-14
99. Lobmeyer MT, Wang L, Zineh I, et al. Polymorphisms in genes coding for GRK2 and GRK5 and response differences in antihypertensive-treated patients. Pharmacogenet Genomics 2011;21:42-9
100. Petersen M, Andersen JT, Hjelvang BR, et al. Association of beta-adrenergic receptor polymorphisms and mortality in carvedilol-treated chronic heart-failure patients. Br J Clin Pharmacol 2011;71:556-65
101. Klenke S, Kussmann M, Siffert W. The GNB3 C825T polymorphism as a pharmacogenetic marker in the treatment of hypertension, obesity, and depression. Pharmacogenet Genomics 2011;21:594-606
102. Bagos PG, Elefsinioti AL, Nikolopoulos GK, et al. The GNB3 C825T polymorphism and essential hypertension: a meta-analysis of 34 studies including 14,094 cases and 17,760 controls. J Hypertens 2007;25:487-500 (Pubitemid 46213782)
103. Jia H, Hingorani AD, Sharma P, et al. Association of the G(s)alpha gene with essential hypertension and response to beta-blockade. Hypertension 1999;34:8-14 (Pubitemid 29325711)
104. Kurnik D, Cunningham AJ, Sofowora GG, et al. GRK5 Gln41Leu polymorphism is not associated with sensitivity to beta(1)-adrenergic blockade in humans. Pharmacogenomics 2009;10:1581-7
105. Rafiq S, Anand S, Roberts R. Genome-wide association studies of hypertension: have they been fruitful? J Cardiovasc Transl Res 2010;3:189-96
106. Ehret GB. Genome-wide association studies: contribution of genomics to understanding blood pressure and essential hypertension. Curr Hypertens Rep 2010;12:17-25
107. Levy D, Ehret GB, Rice K, et al. Genome-wide association study of blood pressure and hypertension. Nat Genet 2009;41:677-87
108. Newton-Cheh C, Johnson T, Gateva V, et al. Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet 2009;41:666-76
109. Kato N, Takeuchi F, Tabara Y, et al. Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. Nat Genet 2011;43:531-8
110. Dupuis J, Langenberg C, Prokopenko I, et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 2010;42:105-16
111. Rorsman P, Bokvist K, Ammala C, et al. Activation by adrenaline of a low-conductance G protein-dependent K + channel in mouse pancreatic B cells. Nature 1991;349:77-9 (Pubitemid 21912019)
112. Prichard BN, Gillam PM. Use of propranolol (Inderal) in treatment of hypertension. Br Med J 1964;2:725-7
113. Jia H, Sharma P, Hopper R, et al. Beta2-adrenoceptor gene polymorphisms and blood pressure variations in East Anglian Caucasians. J Hypertens 2000;18:687-93 (Pubitemid 30406739)
114. O'Shaughnessy KM, Fu B, Dickerson C, et al. The gain-of-function G389R variant of the beta1-adrenoceptor does not influence blood pressure or heart rate response to beta-blockade in hypertensive subjects. Clin Sci (Lond) 2000;99:233-8
115. 1-AR polymorphisms on blood pressure response to metoprolol.
116. 1-AR polymorphisms on responses to metoprolol.
117. 1-AR polymorphisms on responses to atenolol.
118. Beitelshees AL, Zineh I, Yarandi HN, et al. Influence of phenotype and pharmacokinetics on beta-blocker drug target pharmacogenetics. Pharmacogenomics J 2006;6:174-8 (Pubitemid 43811568)
119. Liu J, Liu ZQ, Yu BN, et al. Beta(1)-adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension. Clin Pharmacol Ther 2006;80:23-32 (Pubitemid 43946840)
120. Sasaguri T, Shiraishi F, Yoshihara T, et al. Beta(1)-Adrenergic receptor gene polymorphisms and the acute response to atenolol in healthy young Japanese subjects. J Pharmacol Sci 2011;115:490-9
121. Filigheddu F, Reid JE, Troffa C, et al. Genetic polymorphisms of the beta-adrenergic system: association with essential hypertension and response to beta-blockade. Pharmacogenomics J 2004;4:154-60 (Pubitemid 38786553)
122. Filigheddu F, Argiolas G, Degortes S, et al. Haplotypes of the adrenergic system predict the blood pressure response to beta-blockers in women with essential hypertension. Pharmacogenomics 2010;11:319-25
123. Karlsson J, Lind L, Hallberg P, et al. Beta1-adrenergic receptor gene polymorphisms and response to beta1-adrenergic receptor blockade in patients with essential hypertension. Clin Cardiol 2004;27:347-50 (Pubitemid 38703089)
124. Suonsyrja T, Donner K, Hannila-Handelberg T, et al. Common genetic variation of beta1- and beta2-adrenergic receptor and response to four classes of antihypertensive treatment. Pharmacogenet Genomics 2010;20:342-5
125. Lee J, Aziz H, Liu L, et al. Beta(1)-adrenergic receptor polymorphisms and response to beta-blockade in the African-American study of kidney disease and hypertension (AASK). Am J Hypertens 2011;24:694-700
126. Pacanowski MA, Gong Y, Cooper-Dehoff RM, et al. Beta-adrenergic receptor gene polymorphisms and beta-blocker treatment outcomes in hypertension. Clin Pharmacol Ther 2008;84:715-21
127. Cohn JN, Levine TB, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984;311:819-23 (Pubitemid 14035089)
128. Bristow MR, Gilbert EM, Abraham WT, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. Circulation 1996;94:2807-16 (Pubitemid 26411745)
129. Hjalmarson A, Goldstein S, Fagerberg B, et al. Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL randomized intervention trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group. JAMA 2000;283:1295-302 (Pubitemid 30129796)
130. Investigators TR. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001-7
131. Terra SG, Hamilton KK, Pauly DF, et al. Beta1-adrenergic receptor polymorphisms and left ventricular remodeling changes in response to beta-blocker therapy. Pharmacogenet Genomics 2005;15:227-34 (Pubitemid 40569894)
132. Chen L, Meyers D, Javorsky G, et al. Arg389Gly-beta1-adrenergic receptors determine improvement in left ventricular systolic function in nonischemic cardiomyopathy patients with heart failure after chronic treatment with carvedilol. Pharmacogenet Genomics 2007;17:941-9 (Pubitemid 350293794)
133. Mialet Perez J, Rathz DA, Petrashevskaya NN, et al. Beta 1-adrenergic receptor polymorphisms confer differential function and predisposition to heart failure. Nat Med 2003;9:1300-5 (Pubitemid 37279854)
134. de Groote P, Helbecque N, Lamblin N, et al. Association between beta-1 and beta-2 adrenergic receptor gene polymorphisms and the response to beta-blockade in patients with stable congestive heart failure. Pharmacogenet Genomics 2005;15:137-42 (Pubitemid 40569899)
135. Metra M, Covolo L, Pezzali N, et al. Role of beta-adrenergic receptor gene polymorphisms in the long-term effects of beta-blockade with carvedilol in patients with chronic heart failure. Cardiovasc Drugs Ther 2010;24:49-60
136. Troncoso R, Moraga F, Chiong M, et al. Gln(27) - >Glubeta(2)- adrenergic receptor polymorphism in heart failure patients: differential clinical and oxidative response to carvedilol. Basic Clin Pharmacol Toxicol 2009;104:374-8
137. Lobmeyer MT, Gong Y, Terra SG, et al. Synergistic polymorphisms of beta1 and alpha2C-adrenergic receptors and the influence on left ventricular ejection fraction response to beta-blocker therapy in heart failure. Pharmacogenet Genomics 2007;17:277-82 (Pubitemid 46668051)
138. Cresci S, Kelly RJ, Cappola TP, et al. Clinical and genetic modifiers of long-term survival in heart failure. J Am Coll Cardiol 2009;54:432-44
139. Biolo A, Clausell N, Santos KG, et al. Impact of beta1-adrenergic receptor polymorphisms on susceptibility to heart failure, arrhythmogenesis, prognosis, and response to beta-blocker therapy. Am J Cardiol 2008;102:726-32
140. Borjesson M, Magnusson Y, Hjalmarson A, et al. A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure. Eur Heart J 2000;21:1853-8
141. White HL, de Boer RA, Maqbool A, et al. An evaluation of the beta-1 adrenergic receptor Arg389Gly polymorphism in individuals with heart failure: a MERIT-HF sub-study. Eur J Heart Fail 2003;5:463-8 (Pubitemid 37021640)
142. Shin J, Lobmeyer MT, Gong Y, et al. Relation of beta(2)-adrenoceptor haplotype to risk of death and heart transplantation in patients with heart failure. Am J Cardiol 2007;99:250-5 (Pubitemid 46072763)
143. Sehnert AJ, Daniels SE, Elashoff M, et al. Lack of association between adrenergic receptor genotypes and survival in heart failure patients treated with carvedilol or metoprolol. J Am Coll Cardiol 2008;52:644-51
144. Magnusson Y, Levin MC, Eggertsen R, et al. Ser49Gly of beta1-adrenergic receptor is associated with effective beta-blocker dose in dilated cardiomyopathy. Clin Pharmacol Ther 2005;78:221-31 (Pubitemid 41254107)
145. 1-AR polymorphism on β-blocker response in heart failure.
146. Liggett SB, Cresci S, Kelly RJ, et al. A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure. Nat Med 2008;14:510-17 Study showing GRK5 polymorphism effects in heart failure.
147. Littlejohn MD, Palmer BR, Richards AM, et al. Ile164 variant of beta2-adrenoceptor does not influence outcome in heart failure but may interact with beta blocker treatment. Eur J Heart Fail 2008;10:55-9
148. Cruickshank JM, Prichard BNC. Beta Blockers in Clinical Practice. Churchill Livingstone; Edinburgh, London, Madrid, Melbourne, New York, Tokyo; 1988
149. Christian H, Bertera FM, Mayer MA, et al. Issues in drug metabolism of major antihypertensive drugs: beta-blockers, calcium channel antagonists and angiotensin receptor blockers. Expert Opin Drug Metab Toxicol 2010;6:199-211
150. Bonow RO, Mann DL, Zipes DP, et al. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. Elsevier, Philadelphia; 2011
151. Stringer RA, Strain-Damerell C, Nicklin P, et al. Evaluation of recombinant cytochrome P450 enzymes as an in vitro system for metabolic clearance predictions. Drug Metab Dispos 2009;37:1025-34
152. Kirchheiner J, Heesch C, Bauer S, et al. Impact of the ultrarapid metabolizer genotype of cytochrome P450 2D6 on metoprolol pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 2004;76:302-12 (Pubitemid 39313120)
153. Johnson JA, Liggett SB. Cardiovascular pharmacogenomics of adrenergic
154. Mahesh Kumar KN, Ramu P, Rajan S, et al. Genetic polymorphisms of beta1 adrenergic receptor and their influence on the cardiovascular responses to metoprolol in a South Indian population. J Cardiovasc Pharmacol 2008;52:459-66
155. Liu ZQ, Liu J, Xiang ZH, et al. Distributive characteristics of Ser49Gly and Gly389Arg genetic polymorphisms of beta1-adrenoceptor in Chinese Han and Dai populations. Acta Pharmacol Sin 2006;27:254-8 (Pubitemid 43171167)
156. Maxwell TJ, Ameyaw MM, Pritchard S, et al. Beta-2 adrenergic receptor genotypes and haplotypes in different ethnic groups. Int J Mol Med 2005;16:573-80
157. Thomas GN, Tomlinson B, Chan JC, et al. The Trp64Arg polymorphism of the beta3-adrenergic receptor gene and obesity in Chinese subjects with components of the metabolic syndrome. Int J Obes Relat Metab Disord 2000;24:545-51 (Pubitemid 30323484)
158. Chen QJ, Lu L, Jin C, et al. Insertion/ insertion genotype of alpha(2B)- adrenergic receptor gene polymorphism is associated with silent myocardial ischemia in patients with type 2 diabetes mellitus. Clin Biochem 2010;43:1201-4
159. Rosskopf D, Manthey I, Siffert W. Identification and ethnic distribution of major haplotypes in the gene GNB3 encoding the G-protein beta3 subunit. Pharmacogenetics 2002;12:209-20 (Pubitemid 34596785)
160. de Groote P, Helbecque N, Lamblin N, et al. Beta-adrenergic receptor blockade and the angiotensin-converting enzyme deletion polymorphism in patients with chronic heart failure. Eur J Heart Fail 2004;6:17-21 (Pubitemid 38169600)