Beta blocker specificity: a building block toward personalized medicine

被引:17
作者
DeGeorge, Brent R., Jr. [1 ]
Koch, Walter J. [1 ]
机构
[1] Thomas Jefferson Univ, Ctr Translat Med, George Zallie & Family Lab Cardiovasc Gene Therap, Dept Med, Philadelphia, PA 19107 USA
关键词
D O I
10.1172/JCI30476
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 [基础医学];
摘要
Drugs known as beta blockers, which antagonize the beta-adrenergic receptor (beta-AR), are an important component of the treatment regimen for chronic heart failure (HF). However, a significant body of evidence indicates that genetic heterogeneity at the level of the beta(1)-AR may be a factor in explaining the variable responses of HF patients to beta blockade. In this issue of the JCI, Rochais et al. describe how a single amino acid change in beta(1)-AR alters its structural conformation and improves its functional response to carvedilol, a beta blocker currently used in the treatment of HF (see the related article beginning on page 229). This may explain why some HF patients have better responses not only to carvedilol but to certain other beta blockers as well. The data greatly enhance our mechanistic understanding of myocardial adrenergic signaling and support the development of "tailored" or "personalized" medicine, in which specific therapies could be prescribed based on a patient's genotype.
引用
收藏
页码:86 / 89
页数:4
相关论文
共 18 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]
G protein-coupled receptors:: In silico drug discovery in 3D [J].
Becker, OM ;
Marantz, Y ;
Shacham, S ;
Inbal, B ;
Heifetz, A ;
Kalid, O ;
Bar-Haim, S ;
Warshaviak, D ;
Fichman, M ;
Noiman, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (31) :11304-11309
[3]
Recent developments in constitutive receptor activity and inverse agonism, and their potential for GPCR drug discovery [J].
Bond, RA ;
IJzerman, AP .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2006, 27 (02) :92-96
[4]
Braunwald E, 2000, CIRCULATION, V102, P14
[5]
Eichhorn E, 2001, NEW ENGL J MED, V344, P1659
[6]
Review - The fluorescent toolbox for assessing protein location and function [J].
Giepmans, BNG ;
Adams, SR ;
Ellisman, MH ;
Tsien, RY .
SCIENCE, 2006, 312 (5771) :217-224
[7]
LEE TH, 2001, HEART DIS TXB CARDIO, V101, P652
[8]
Beta-adrenergic receptor polymorphism in human cardiovascular disease [J].
Leineweber, K .
ANNALS OF MEDICINE, 2004, 36 :64-69
[9]
Common polymorphisms of β1-adrenoceptor:: identification and rapid screening assay [J].
Maqbool, A ;
Hall, AS ;
Ball, SG ;
Balmforth, AJ .
LANCET, 1999, 353 (9156) :897-897
[10]
A gain-of-function polymorphism in a G-protein coupling domain of the human β1-adrenergic receptor [J].
Mason, DA ;
Moore, JD ;
Green, SA ;
Liggett, SB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (18) :12670-12674