Pharmacogenetics of heart failure: evidence, opportunities, and challenges for cardiovascular pharmacogenomics.
Heart failure is a significant medical problem affecting more than five million people in the USA alone. Although clinical trials of pharmacological agents have demonstrated significant reductions in the relative risk of mortality across populations, absolute mortality remains high. In addition, individual variation in response is great. Some of this variation may be explained by genetic polymorphism. In this paper, we review the key studies to date in heart failure pharmacogenetics, setting this against a background of recent progress in the genetics of warfarin metabolism. Several polymorphisms that have supporting molecular and clinical data in the heart failure literature are reviewed, among them the beta1-adrenergic receptor variant Arg389Gly and the angiotensin converting enzyme gene insertion/deletion polymorphism. These variants and others are responsible for a fraction of the total variation seen in the treatment response to heart failure. With the dawn of the genomic age, further pharmacogenetic and new pharmacogenomic studies will advance our ability to tailor the treatment of heart failure.
Wheeler
Matthew T
MT
Division of Cardiovascular Medicine, Department of Medicine, Stanford University, 300 Pasteur Drive, Falk CVRC MC 5406, Stanford, CA 94305, USA.
Ho
Michael
M
Knowles
Joshua W
JW
Pavlovic
Aleks
A
Ashley
Euan A
EA
D001711:Biotransformation / Q000235:genetics; D002317:Cardiovascular Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D014644:Genetic Variation; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D016896:Treatment Outcome
D002317:Cardiovascular Agents; D011943:Receptors, Adrenergic, beta