GMKBAMIA Joint Summits on Translational Science proceedings – This study compares multiple phenotyping approaches for identifying statin-related myotoxicity to highlight potential best practices for identifying adverse drug events. Statins are widely used drugs that decrease risk for cardiovascular disease. Muscle toxicity is the most common side effect (1–5% in randomized controlled trials, 9–20% in observational studies) and reason for statin cessation. Statin-induced myotoxicity is an excellent case study for the challenges involved in phenotyping adverse drug events as it falls along a spectrum of reactions from simple muscle pain to severe muscle break down.
Report of New Haplotype for ABCC2 Gene
The Journal of Molecular Diagnostics – The ATP-binding cassette, subfamily C [CFTR/MRP], member 2 (ABCC2) gene is a member of the ATP-binding cassette transporters and is involved in the transport of molecules across cellular membranes. Substrates transported by ABCC2 include antiepileptics, statins, tenofovir, cisplatin, irinotecan, and carbamazepine. Because of the pharmacogenomics implications, we developed a clinical laboratory–developed assay to test for seven variants in the ABCC2 gene: c.3563T>A (p.V1188E, rs17222723), c.1249G>A (p.V417I, rs2273697), c.3972C>T (p.I1324I, rs3740066), c.2302C>T (p.R768W, rs56199535), c.2366C>T (p.S789F, rs56220353), c.-24C>T (5′UTR, rs717620), and c.4544G>A (p.C1515Y, rs8187710)
Loss of Heterozygosity at the CYP2D6 Locus in Breast Cancer: Implications for Tamoxifen Pharmacogenetic Studies
Journal of the National Cancer Institute – Loss of functional genetic polymorphisms in CYP2D6 lead to the absence of functional CYP2D6 protein in approximately 5% to 10% of whites (people of European ancestry) and 1% to 2% of those of Asian and African ancestry. In the literature, these are commonly referred to as CYP2D6–poor metabolizers (PMs). The first study to report an association between CYP2D6polymorphisms and endoxifen plasma concentration was published in 2003 and showed that CYP2D6 PMs exhibited lower endoxifen plasma concentrations than those with functional CYP2D6 enzyme. The results from this study served as an impetus to investigate the influence of CYP2D6 gene variation on clinical outcomes with tamoxifen.
Incorporating temporal EHR data in predictive models for risk stratification of renal function deterioration
Journal of Biomedical Informatics – In this paper, we describe and evaluate three different approaches that use machine learning to build predictive models using temporal EHR data of a patient.
Effect of Genetic African Ancestry on eGFR and Kidney Disease
Journal of the American Society of Nephrology – Self-reported ancestry, genetically determined ancestry, and APOL1 polymorphisms are associated with variation in kidney function and related disease risk, but the relative importance of these factors remains unclear.
Emerging Roles for Pharmacists in Clinical Implementation of Pharmacogenomics
Pharmacotherapy – Pharmacists are uniquely qualified to play essential roles in the clinical implementation of pharmacogenomics. However, specific responsibilities and resources needed for these roles have not been defined. We describe roles for pharmacists that emerged in the clinical implementation of genotype-guided clopidogrel therapy in the University of Florida Health Personalized Medicine Program, summarize preliminary program results, and discuss education, training, and resources needed to support such programs. Planning for University of Florida Health Personalized Medicine Program began in summer 2011 under leadership of a pharmacist, with clinical launch in June 2012 of a clopidogrel-CYP2C19 pilot project aimed at tailoring antiplatelet therapies for patients undergoing percutaneous coronary intervention and stent placement.
Prerequisites to Implementing a Pharmacogenomics Program in a Large Healthcare System
Clinical Pharmacology & Therapeutics – Pharmacogenomics (PGx) technology is advancing rapidly; however, clinical adoption is lagging. The Indiana Institute of Personalized Medicine (IIPM) places a strong focus on translating PGx research into clinical practice. We will describe what have been found to be the key requirements that must be delivered in order to ensure a successful and enduring PGx implementation within a large healthcare system.
Warfarin Pharmacogenetics
Trends in Cardiovascular Medicine – Since its approval in 1954, warfarin has been widely prescribed for the prophylaxis and treatment of venous thromboembolism and complications associated with atrial fibrillation and cardiac valve replacement. Even with the availability of newer agents shown to be noninferior to warfarin, warfarin remains the most commonly prescribed oral anticoagulant.
Use of a patient-entered Family Health History Tool with Decision Support in Primary Care: Impact of Identification of Increased Risk Patients on Genetic Counseling Attendance
Journal of Genetic Counseling – Although MeTree identified a significant proportion of patients for whom GC was recommended, persistent barriers indicate the need for improved referral processes and patient and physician education about the benefits of GC.
Use of a Patient‐Entered Family Health History Tool with Decision Support in Primary Care: Impact of Identification of Increased Risk Patients on Genetic Counseling Attendance
Journal of Genetic Counseling – Several barriers inhibit collection and use of detailed family health history (FHH) in primary care. MeTree, a computer‐based FHH intake and risk assessment tool with clinical decision support, was developed to overcome these barriers. Here, we describe the impact of MeTree on genetic counseling (GC) referrals and attendance.