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It has been estimated that genetic differences may account for 20-95% of the variation in an individual's response to medications [1]. Pharmacogenomics, the study of genetic variations that influence a patient's response to drugs, has the potential to individualize drug therapy. Knowledge of a patient's genetic variation may decrease the chance for an adverse drug reaction as well as increase the effectiveness of drug therapy which may have a significant impact on patient outcomes. Pharmacogenomics can identify individuals that are poor metabolizers of drugs and individuals that are ultra rapid metabolizers. These differences in metabolism can impact both the likelihood for drug toxicity and efficacy of a therapeutic regimen. The Institute of Medicine estimated that adverse drug reactions may affect up to 1.5 million patients per year leading to increased hospitalizations, death and higher health care costs [2]. Therefore, knowledge of a patient's pharmacogenomic profile has the potential to improve efficacy of pharmacological therapeutics as well as decrease adverse drug reactions.
Examples for cardiovascular therapeutics
Clopidogrel is an example of a commonly used medication in cardiology where knowledge of the pharmacogenomic profile of a patient may have a profound impact on outcomes. Clopidogrel is a platelet P2Y12 receptor blocker used with aspirin for patients presenting with an acute coronary syndrome or after placement of a coronary stent to reduce subsequent cardiac events or prevent stent thrombosis. Clinical studies of platelet function have shown that 16 to 50% of patients may have resistance or are nonresponders to clopidogrel treatment [3]. This response variability may be due in part to variability in the generation of an active metabolite. Clopidogrel is a prodrug and is converted to its active metabolite by the hepatic cytochrome P450 enzymatic system. The CYP2C19 isoform is a key enzyme in the activation pathway for clopidogrel. Several CYP2C19 variants are associated with loss-of-function of the enzyme. A number of major clinical trials using clopidogrel after an acute coronary syndrome and coronary stent placement have shown that patients with genetic polymorphisms conferring CYP2C19 loss-of-function increase the risk of adverse outcomes [4-7]. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has released guidelines on appropriate indication for CYP2C19 genotype-directed therapy with recommendations linked to specific CYP2C19 alleles [8]. At this point in time, the American Heart Association/American...