TY - JOUR
T1 - Mechanisms of pharmacogenomic effects of genetic variation within the cardiac adrenergic network in heart failure
AU - Dorn, Gerald W.
AU - Liggett, Stephen B.
PY - 2009/9
Y1 - 2009/9
N2 - One of the goals of pharmacogenomics is the use of genetic variants to predict an individual's response to treatment. Although numerous candidate and genome-wide associations have been made for cardiovascular response-outcomes, little is known about how a given polymorphism imposes the phenotype. Such mechanisms are important, because they tie the observed human response to specific signaling alterations and thus provide cause-and-effect relationships, aid in the design of hypothesis-based clinical studies, can help to devise work-around drugs, and can reveal new aspects of the pathophysiology of the disease. Here we discuss polymorphisms within the adrenergic receptor network in the context of heart failure and β-adrenergic receptor blocker therapy, where multiple approaches to understand the mechanism have been undertaken. We propose a comprehensive series of studies, ranging from transfected cells, transgenic mice, and ex vivo and in vitro human studies as a model approach to explore mechanisms of action of pharmacogenomic effects and extend the field beyond observational associations.
AB - One of the goals of pharmacogenomics is the use of genetic variants to predict an individual's response to treatment. Although numerous candidate and genome-wide associations have been made for cardiovascular response-outcomes, little is known about how a given polymorphism imposes the phenotype. Such mechanisms are important, because they tie the observed human response to specific signaling alterations and thus provide cause-and-effect relationships, aid in the design of hypothesis-based clinical studies, can help to devise work-around drugs, and can reveal new aspects of the pathophysiology of the disease. Here we discuss polymorphisms within the adrenergic receptor network in the context of heart failure and β-adrenergic receptor blocker therapy, where multiple approaches to understand the mechanism have been undertaken. We propose a comprehensive series of studies, ranging from transfected cells, transgenic mice, and ex vivo and in vitro human studies as a model approach to explore mechanisms of action of pharmacogenomic effects and extend the field beyond observational associations.
UR - http://www.scopus.com/inward/record.url?scp=69549106507&partnerID=8YFLogxK
U2 - 10.1124/mol.109.056572
DO - 10.1124/mol.109.056572
M3 - Short survey
C2 - 19491328
AN - SCOPUS:69549106507
SN - 0026-895X
VL - 76
SP - 466
EP - 480
JO - Molecular pharmacology
JF - Molecular pharmacology
IS - 3
ER -