Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Mar;13(4):465-75.
doi: 10.2217/pgs.12.2.

Clinical utility of pharmacogenetic biomarkers in cardiovascular therapeutics: a challenge for clinical implementation

Frank S Ong  1 , Joshua L Deignan, Jane Z Kuo, Kenneth E Bernstein, Jerome I Rotter, Wayne W Grody, Kingshuk Das
Affiliations
Review

Clinical utility of pharmacogenetic biomarkers in cardiovascular therapeutics: a challenge for clinical implementation

Frank S Ong et al. Pharmacogenomics. 2012 Mar.

Abstract

In the past decade, significant strides have been made in the area of cardiovascular pharmacogenomic research, with the discovery of associations between certain genotypes and drug-response phenotypes. While the motivations for personalized and predictive medicine are promising for patient care and support a model of health system efficiency, the implementation of pharmacogenomics for cardiovascular therapeutics on a population scale faces substantial challenges. The greatest obstacle to clinical implementation of cardiovascular pharmacogenetics may be the lack of both reproducibility and agreement about the validity and utility of the findings. In this review, we present the scientific evidence in the literature for diagnostic variants for the US FDA-labeled cardiovascular therapies, namely CYP2C19 and clopidogrel, CYP2C9/VKORC1 and warfarin, and CYP2D6/ADRB1 and β-blockers. We also discuss the effect of HMGCR/LDLR in decreasing the effectiveness of low-density lipoprotein cholesterol with statin therapy, the SLCO1B1 genotype and simvastatin myotoxicity, and ADRB1/ADD1 for antihypertensive response.

PubMed Disclaimer

References

    1. Ong FS, Grody WW, Deignan JL. Privacy and data management in the era of massively parallel next-generation sequencing. Expert Rev Mol Diagn. 2011;11(5):457–459. Discusses ethical, privacy and social issues in the era of massively parallel next-generation sequencing. - PMC - PubMed
    1. Savi P, Combalbert J, Gaich C, et al. The antiaggregating activity of clopidogrel is due to a metabolic activation by the hepatic cytochrome P450-1A. Thromb Haemost. 1994;72(2):313–317. - PubMed
    1. Turpeinen M, Tolonen A, Uusitalo J, Jalonen J, Pelkonen O, Laine K. Effect of clopidogrel and ticlopidine on cytochrome P450 2B6 activity as measured by bupropion hydroxylation. Clin Pharmacol Ther. 2005;77(6):553–559. - PubMed
    1. Richter T, Murdter TE, Heinkele G, et al. Potent mechanism-based inhibition of human CYP2B6 by clopidogrel and ticlopidine. J Pharmacol Exp Ther. 2004;308(1):189–197. - PubMed
    1. O’Donoghue M, Wiviott SD. Clopidogrel response variability and future therapies: clopidogrel: does one size fit all? Circulation. 2006;114(22):e600–e606. - PubMed

Websites

    1. Table of pharmacogenomic biomarkers in drug labels. www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm0833.... - PubMed
    1. Label and approval history, clopidogrel bisulfate. www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm2362....
    1. ELEVATE-TIMI 56 (NCT01235351) http://clinicaltrials.gov/ct2/show/NCT01235351.
    1. Label and approval history, warfarin sodium, CYP2C9. www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm2380....
    1. Label and approval history, warfarin sodium, VKORC1. www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm2380....

Publication types

MeSH terms