title: Clinical utility of pharmacogenetic biomarkers in cardiovascular therapeutics: a challenge for clinical implementation.
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.
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. frank.ong@cshs.org
authors.forename: Frank S
authors.initials: FS
authors.lastname: Ong
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Deignan
authors.forename: Jane Z
authors.initials: JZ
authors.lastname: Kuo
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Bernstein
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Grody
authors.forename: Kingshuk
authors.initials: K
authors.lastname: Das
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000235:genetics*; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D054316:Biomarkers, Pharmacological; D014859:Warfarin; D000077144:Clopidogrel; D013988:Ticlopidine