Candidate-Gene Study of Functional Polymorphisms in SLCO1B1 and CYP3A4/5 and the Cholesterol-Lowering Response to Simvastatin.

Cholesterol-lowering response to 40 mg simvastatin daily for 6 weeks was examined for associations with common genetic polymorphisms in key genes affecting simvastatin metabolism (CYP3A4 and CYP3A5) and transport (SLCO1B1). In white people (n = 608), SLCO1B1 521C was associated with lesser reductions of total and low-density lipoprotein cholesterol. Associations between SLCO1B1 521C and cholesterol response were not detected in African Americans (n = 333). Associations between CYP3A4*22 or CYP3A5*3 and cholesterol response were not detected in either race, and no significant race-gene or gene-gene interactions were detected. As several of the analyses may have been underpowered (especially the analyses in the African American cohort), the findings not suggesting an association should not be considered conclusive and warrant further investigation. The finding regarding SLCO1B1 521C in whites was consistent with several previous reports. SLCO1B1 521C resulted in a diminished cholesterol-lowering response, but a marginal effect size limits utility for predicting simvastatin response.

The Pharmacogenomics Research Network Translational Pharmacogenetics Program: Outcomes and Metrics of Pharmacogenetic Implementations Across Diverse Healthcare Systems.

Numerous pharmacogenetic clinical guidelines and recommendations have been published, but barriers have hindered the clinical implementation of pharmacogenetics. The Translational Pharmacogenetics Program (TPP) of the National Institutes of Health (NIH) Pharmacogenomics Research Network was established in 2011 to catalog and contribute to the development of pharmacogenetic implementations at eight US healthcare systems, with the goal to disseminate real-world solutions for the barriers to clinical pharmacogenetic implementation. The TPP collected and normalized pharmacogenetic implementation metrics through June 2015, including gene-drug pairs implemented, interpretations of alleles and diplotypes, numbers of tests performed and actionable results, and workflow diagrams. TPP participant institutions developed diverse solutions to overcome many barriers, but the use of Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines provided some consistency among the institutions. The TPP also collected some pharmacogenetic implementation outcomes (scientific, educational, financial, and informatics), which may inform healthcare systems seeking to implement their own pharmacogenetic testing programs.