Pharmacogenetic considerations in diseases of cardiac ion channels.
Phenotypic variation within a species arises from differences in genetic makeup between individuals. This inherent diversity empowers the species as a whole to explore and expand into new environmental niches and also to survive new stressors within an ever-changing environment. Paradoxically, one class of stressors currently challenging the human population is therapeutic drugs: medications designed to combat disease are often associated with a host of nonspecific side effects. Following earlier studies of the involvement of some cardiac ion currents in unwanted drug interactions, recent reports have identified not only the ion channel subunits involved but also a range of mutations and single nucleotide polymorphisms in ion channel genes that predispose to both drug-induced and familial cardiac arrhythmia. The tendency for individuals harboring specific, often common, gene variants to succumb to life-threatening cardiac arrhythmia, and the contribution of other factors such as drug interaction to disease etiology in these cases, are discussed here together with potential pharmacogenetic strategies for arrhythmia circumvention and therapy.
Anantharam
Arun
A
Division of Cardiology, Dept. of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
Markowitz
Steven M
SM
Abbott
Geoffrey W
GW
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D003638:Deafness / Q000235:genetics / Q000503:physiopathology; D015316:Genetic Therapy; D006321:Heart / Q000187:drug effects; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008133:Long QT Syndrome / Q000235:genetics / Q000503:physiopathology; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D010597:Pharmacogenetics
D007473:Ion Channels