β-1 and β-2 adrenoceptor polymorphisms:: Functional importance, impact on cardiovascular diseases and drug responses

被引:100
作者
Brodde, Otto-Erich [1 ]
机构
[1] Univ Essen Gesamthsch, Sch Med, Dept Pathophysiol, D-45147 Essen, Germany
关键词
D O I
10.1016/j.pharmthera.2007.07.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
beta-1 and beta-2 adrenoceptors (AR) play a pivotal role in regulation of the activity of the sympathetic nervous system and agonists and antagonists at both beta AR subtypes are frequently used in treatment of cardiovascular diseases. Both beta-1 and beta-2 AR genes have several polymorphisms that encode different amino acids. This review summarizes new insights into the functional importance of these polymorphisms, as well as their relationship to cardiovascular diseases and their impact on responses to adrenergic drug treatment. At present, it seems that, for cardiovascular diseases, beta-1 and beta-2 AR polymorphisms do not play a role as disease-causing genes; they might, however, be associated with disease-related phenotypes. In addition they could influence adrenergic drug responses. Thus, the Arg(389)Gly beta-1 AR polymorphism might predict responsiveness to beta-1 AR agonist and blocker treatment: patients homozygous for the Arg(389) beta-1 AR polymorphism should be good responders, while patients homozygous for the Gly(389) beta-1 AR polymorphism should be poor or nonresponders. Furthermore, the Arg(16)Gln(27) beta-2 AR seems to have strong impact on long-term agonist-induced beta-2 AR desensitization. Thus, patients carrying this haplotype appear to suffer from rapid loss of therapeutic efficacy of chronic agonist treatment, as has been demonstrated in asthma patients. Moreover, the Arg(16)Glu(27) beta-2 AR haplotype might have some predictive value for poor outcome of heart failure. Future large prospective studies have to replicate these findings in order to reach the final goal of pharmacogenomic research: to optimize and individualize drug therapy based on the patient's genetic determinants of drug efficacy. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:1 / 29
页数:29
相关论文
共 193 条
[1]   Myocardial β1-adrenergic receptor polymorphisms affect functional recovery after ischemic injury [J].
Akhter, SA ;
D'Souza, KM ;
Petrashevskaya, NN ;
Mialet-Perez, J ;
Liggett, SB .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2006, 290 (04) :H1427-H1432
[2]   Pharmacogenetics of antihypertensive treatment [J].
Arnett, DK ;
Claas, SA ;
Glasser, SP .
VASCULAR PHARMACOLOGY, 2006, 44 (02) :107-118
[3]   Interactive effects of common β2-adrenoceptor haplotypes and age on susceptibility to hypertension and receptor function [J].
Bao, XP ;
Mills, PJ ;
Rana, BK ;
Dimsdale, JE ;
Schork, NJ ;
Smith, DW ;
Rao, FW ;
Milic, M ;
O'Connor, DT ;
Ziegler, MG .
HYPERTENSION, 2005, 46 (02) :301-307
[4]   Thr164Ile polymorphism of β2-adrenergic receptor negatively modulates cardiac contractility:: implications for prognosis in patients with idiopathic dilated cardiomyopathy [J].
Barbato, Emanuele ;
Penicka, Martin ;
Delrue, Leen ;
Van Durme, Frederic ;
De Bruyne, Bernard ;
Goethals, Marc ;
Wijns, William ;
Vanderheyden, Marc ;
Bartunek, Jozef .
HEART, 2007, 93 (07) :856-861
[5]   Polymorphism in the β1-adrenergic receptor gene and hypertension [J].
Bengtsson, K ;
Melander, O ;
Orho-Melander, M ;
Lindblad, U ;
Ranstam, J ;
Råstam, L ;
Groop, L .
CIRCULATION, 2001, 104 (02) :187-190
[6]   β2-adrenergic receptor gene variation and hypertension in subjects with type 2 diabetes [J].
Bengtsson, K ;
Orho-Melander, M ;
Melander, O ;
Lindblad, U ;
Ranstam, J ;
Råstam, L ;
Groop, L .
HYPERTENSION, 2001, 37 (05) :1303-1308
[7]   BETA-ADRENERGIC RECEPTORS IN HUMAN MYOMETRIUM DURING PREGNANCY - CHANGES IN THE NUMBER OF RECEPTORS AFTER BETA-MIMETIC TREATMENT [J].
BERG, G ;
ANDERSSON, RGG ;
RYDEN, G .
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 1985, 151 (03) :392-396
[8]   A novel polymorphism in the gene coding for the beta1-adrenergic receptor associated with survival in patients with heart failure [J].
Börjesson, M ;
Magnusson, Y ;
Hjalmarson, Å ;
Andersson, B .
EUROPEAN HEART JOURNAL, 2000, 21 (22) :1853-1858
[9]   Positional genomic analysis identifies the β2-adrenergic receptor gene as a susceptibility locus for human hypertension [J].
Bray, MS ;
Krushkal, J ;
Li, L ;
Ferrell, R ;
Kardia, S ;
Sing, CF ;
Turner, ST ;
Boerwinkle, E .
CIRCULATION, 2000, 101 (25) :2877-2882
[10]   Feedback inhibition of catecholamine release by two different α2-adrenoceptor subtypes prevents progression of heart failure [J].
Brede, M ;
Wiesmann, F ;
Jahns, R ;
Hadamek, K ;
Arnolt, C ;
Neubauer, S ;
Lohse, MJ ;
Hein, L .
CIRCULATION, 2002, 106 (19) :2491-2496