Clinical utility of pharmacogenetic biomarkers in cardiovascular therapeutics: a challenge for clinical implementation. (March 2012)

• Record Type: Journal Article
• Authors: Ong, Frank S; Deignan, Joshua L; Kuo, Jane Z; Bernstein, Kenneth E; Rotter, Jerome I; Grody, Wayne W; Das, Kingshuk
• Is Part Of: Pharmacogenomics. Volume 13:Number 4(2012)
• Page Start: 465
• Page End: 475
• Publication Date: 2012-03
• Subjects: biomarker -- cardiovascular -- clinical utility -- clopidogrel -- drug label -- genetics -- personalized medicine -- pharmacogenetics -- predictive medicine -- warfarin; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.12.2
• Languages: English
• ISSNs: 1462-2416

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 ββ-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.