Recent developments and future directions for the use of pharmacogenomics in cardiovascular disease treatments

ABSTRACT

Introduction: Cardiovascular disease is still the leading cause of death worldwide. There are many environmental and genetic factors that play a role in the development of cardiovascular disease. The treatment of cardiovascular disease is beginning to move in the direction of personalized medicine by using biomarkers from the patient’s genome to design more effective treatment plans. Pharmacogenomics have already uncovered many links between genetic variation and response of many different drugs.

Areas covered: This article will focus on the main polymorphisms that impact the risk of adverse effects and response efficacy of statins, clopidogrel, aspirin, β-blockers, warfarin dalcetrapib and vitamin E. The genes discussed include SLCO1B1, ABCB1, CYP3A4, CYP3A5, CYP2C19, PTGS1, PTGS2, ADRB1, ADCY9, CYP2C19, PON1, CES1, PEAR1, GPIIIa, CYP2D6, CKORC1, CYP2C9 and Hp.

Expert opinion: Although there are some convincing results that have already been incorporated in the labelling treatment guidelines, most gene-drug relationships have been inconsistent. A better understanding of the relationships between genetic factors and drug response will provide more opportunities for personalized diagnosis and treatment of cardiovascular disease.

KEYWORDS:

• Aspirin
• β-blocker
• clopidogrel
• cardiovascular disease
• dalcetrapib
• pharmacogenomics
• polymorphism
• statin
• vitamin E
• warfarin

Article highlights

• Genetic variation in the SLCO1B1, ABCB1, CYP3A4, and CYP3A5 genes have been shown to affect the risk of adverse events and response during statin therapy.

• There is data that suggests that certain polymorphisms could be valuable biomarkers in predicting response to β-blocker therapy and anti-platelet therapy resistance.

• Although the dal-OUTCOME trial failed to show that dalcetrapib provides a benefit, subsequent analysis has revealed that individuals with a specific ADCY9 polymorphism might benefit from dalcetrapib therapy.

• Meta-analysis of various trials and a small prospective randomized control trial have demonstrated that DM and the Hp2-2 haplotype can serve as an effective biomarker to predict a beneficial response to vitamin E therapy

• Pharmacogenomics has the potential to move cardiovascular disease care towards personal medicine by helping to identify patients who will have an adverse response and those that will benefit from a specific therapy.

• Pharmacogenomics has the potential to enhance drug development by lowering the costs and risks of drug development and testing.

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Declaration of interest

A Levy is the author of a patent, which claims to predict the ability of the haptoglobin genotype to predict benefit from vitamin E in individuals with diabetes. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

Funding for this paper was provided by the Israel Science Foundation Grant #190/16