Adrenergic signaling polymorphisms and their impact on cardiovascular disease.
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 beta-adrenergic receptor antagonists (beta-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 beta-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.
Dorn
Gerald W
GW
Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. gdorn@dom.wustl.edu
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D002319:Cardiovascular System / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D011110:Polymorphism, Genetic; D011941:Receptors, Adrenergic / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic