GMKBCurrent Hypertension Report – Heart disease is a leading cause of death in the United States, and hypertension is a predominant risk factor. Thus, effective blood pressure control is important to prevent adverse sequelae of hypertension, including heart failure, coronary artery disease, atrial fibrillation, and ischemic stroke. Over half of Americans have uncontrolled blood pressure, which may in part be explained by interpatient variability in drug response secondary to genetic polymorphism.
Genetics of Resistant Hypertension: a Novel Pharmacogenomics Phenotype
Current Hypertension Report – Resistant hypertension (RHTN), defined as an uncontrolled blood pressure despite the use of multiple antihypertensive medications, is an increasing clinical problem associated with increased cardiovascular (CV) risk, including stroke and target organ damage.
A conceptual model for translating omic data into clinical action
Journal of Pathology Informatics – Here, we outline a conceptual model for the application of omic data in the clinical context, called “the omic funnel.”
Attitudes of Clinicians Following Large-Scale Pharmacogenomics Implementation
Pharmacogenomics Journal – Clinician attitudes towards multiplexed genomic testing may be vital to the success of translational programs. We surveyed clinicians at an academic medical center about their views on a large pharmacogenomics implementation, the PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care & Treatment) program.
Cypiripi: exact genotyping of CYP2D6 using high-throughput sequencing data
Bioinformatics – Response to a large number of clinically prescribed drugs varies significantly among individuals. Although some patients show a good response to a medication, the same treatment might fail in others or cause serious side effects, which can even result in the death of the patient (Ma and Lu, 2011). In many cases, an individual’s genetic makeup has been recognized as one of the potential causes of treatment failures
Pharmacogenomics in cardiology – genetics and drug response: 10 years of progress
Future Cardiology – Following completion of the Human Genome Project in 2003, Dr Francis Collins and others on behalf of the National Human Genome Research Institute announced their vision for the future of genomics research. A number of grand challenges were identified, and among these were developing strategies to identify genetic contributions to drug response, creating genome-based approaches to predict drug response, and applying discoveries to promote the use of genomic information into clinical practice. The NIH has invested significant resources in addressing these challenges, including funding the International HapMap and 1000 Genomes Projects, which have enabled genome-wide association studies (GWAS) of drug response.
Personalized medicine in diabetes mellitus: current opportunities and future prospects
Annals of the New York Academy of sciences – Currently, there are 382 million people living with diabetes mellitus around the world, and the total number is predicted to increase by over 50% over the next 20 years. Diabetes mellitus is a spectrum of metabolic disorders characterized by hyperglycemia. Poorly controlled diabetes mellitus can lead to microvascular and macrovascular complications, including kidney failure, blindness, amputation, and cardiovascular disease. Fortunately, medical advances have increased the number of treatment options for diabetes and improved outcomes for many individuals. However, there remains a need to determine the appropriate therapy for each individual, since a significant number of monotherapy treatments fail within 3 years and diabetes-related morbidity and mortality continue.
Phenotyping Adverse Drug Reactions: Statin-Related Myotoxicity
AMIA 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.