TY - JOUR
T1 - Adrenergic signaling polymorphisms and their impact on cardiovascular disease
AU - Dorn, Gerald W.
PY - 2010/7
Y1 - 2010/7
N2 - This review examines the impact of recent discoveries defining personal genetics of adrenergic signaling polymorphisms on scientific discovery and medical practice related to cardiovascular diseases. The adrenergic system is the major regulator of minute-by-minute cardiovascular function. Inhibition of adrenergic signaling with pharmacological β-adrenergic receptor antagonists (β-blockers) is first-line therapy for heart failure and hypertension. Advances in pharmacology, molecular biology, and genetics of adrenergic signaling pathways have brought us to the point where personal genetic differences in adrenergic signaling factors are being assessed as determinants of risk or progression of cardiovascular disease. For a few polymorphisms, functional data generated in cell-based systems, genetic mouse models, and pharmacological provocation of human subjects are concordant with population studies that suggest altered risk of cardiovascular disease or therapeutic response to β-blockers. For the majority of adrenergic pathway polymorphisms however, published data conflict, and the clinical relevance of individual genotyping remains uncertain. Here, the current state of laboratory and clinical evidence that adrenergic pathway polymorphisms can affect cardiovascular pathophysiology is comprehensively reviewed and compared, with a goal of placing these data in the broad context of potential clinical applicability.
AB - This review examines the impact of recent discoveries defining personal genetics of adrenergic signaling polymorphisms on scientific discovery and medical practice related to cardiovascular diseases. The adrenergic system is the major regulator of minute-by-minute cardiovascular function. Inhibition of adrenergic signaling with pharmacological β-adrenergic receptor antagonists (β-blockers) is first-line therapy for heart failure and hypertension. Advances in pharmacology, molecular biology, and genetics of adrenergic signaling pathways have brought us to the point where personal genetic differences in adrenergic signaling factors are being assessed as determinants of risk or progression of cardiovascular disease. For a few polymorphisms, functional data generated in cell-based systems, genetic mouse models, and pharmacological provocation of human subjects are concordant with population studies that suggest altered risk of cardiovascular disease or therapeutic response to β-blockers. For the majority of adrenergic pathway polymorphisms however, published data conflict, and the clinical relevance of individual genotyping remains uncertain. Here, the current state of laboratory and clinical evidence that adrenergic pathway polymorphisms can affect cardiovascular pathophysiology is comprehensively reviewed and compared, with a goal of placing these data in the broad context of potential clinical applicability.
UR - http://www.scopus.com/inward/record.url?scp=77955612761&partnerID=8YFLogxK
U2 - 10.1152/physrev.00001.2010
DO - 10.1152/physrev.00001.2010
M3 - Review article
C2 - 20664078
AN - SCOPUS:77955612761
SN - 0031-9333
VL - 90
SP - 1013
EP - 1062
JO - Physiological reviews
JF - Physiological reviews
IS - 3
ER -