Race and Drug Toxicity: A Study of Three Cardiovascular Drugs with Strong Pharmacogenetic Recommendations.

The Clinical Pharmacogenetics Implementation Consortium (CPIC) establishes evidence-based guidelines for utilizing pharmacogenetic information for certain priority drugs. Warfarin, clopidogrel and simvastatin are cardiovascular drugs that carry strong prescribing guidance by CPIC. The respective pharmacogenes for each of these drugs exhibit considerable variability amongst different ethnic/ancestral/racial populations.

Genome Wide Epistasis Study of On-Statin Cardiovascular Events with Iterative Feature Reduction and Selection.

Predicting risk for major adverse cardiovascular events (MACE) is an evidence-based practice that incorporates lifestyle, history, and other risk factors. Statins reduce risk for MACE by decreasing lipids, but it is difficult to stratify risk following initiation of a statin. Genetic risk determinants for on-statin MACE are low-effect size and impossible to generalize.

The ACCOuNT Consortium: A Model for the Discovery, Translation, and Implementation of Precision Medicine in African Americans.

The majority of pharmacogenomic (PGx) studies have been conducted on European ancestry populations, thereby excluding minority populations and impeding the discovery and translation of African American-specific genetic variation into precision medicine. Without accounting for variants found in African Americans, clinical recommendations based solely on genetic biomarkers found in European populations could result in misclassification of drug response in African American patients. To address these challenges, we formed the Transdisciplinary Collaborative Center (TCC), African American Cardiovascular Pharmacogenetic Consortium (ACCOuNT), to discover novel genetic variants in African Americans related to clinically actionable cardiovascular phenotypes and to incorporate African American-specific sequence variations into clinical recommendations at the point of care.

Teaching students in clinical programs about pharmacogenomics: do they understand drug-drug interactions?

Teaching the clinical implementation of pharmacogenomics to students in clinical programs first requires careful consideration of their aptitude in basic clinical pharmacologic concepts. Prior to developing training exercises on drug-gene interactions, educators must first assess student competency in identifying and managing drug-drug interactions given the similarities in identifying and managing these sources of medication error.

Impact of a personal CYP2D6 testing workshop on physician assistant student attitudes toward pharmacogenetics.

Aim: We assessed the impact of personal CYP2D6 testing on physician assistant student competency in, and attitudes toward, pharmacogenetics (PGx).

Materials & Methods: Buccal samples were genotyped for CYP2D6 polymorphisms. Results were discussed during a 3-h PGx workshop.

Novel genetic predictors of venous thromboembolism risk in African Americans.

Venous thromboembolism (VTE) is the third most common life-threatening cardiovascular condition in the United States, with African Americans (AAs) having a 30% to 60% higher incidence compared with other ethnicities. The mechanisms underlying population differences in the risk of VTE are poorly understood. We conducted the first genome-wide association study in AAs, comprising 578 subjects, followed by replication of highly significant findings in an independent cohort of 159 AA subjects.

Genetic Variation in CYP2R1 and GC Genes Associated With Vitamin D Deficiency Status.

This cross-sectional study enrolled 180 patients at a private family practice in Virginia. Total serum vitamin D concentrations were obtained weekly from January 30, 2013, through March 30, 2013, in consecutive patients regularly scheduled for laboratory work at the practice. Patients were categorized into 2 groups and analyzed for variant alleles in vitamin D receptor ( VDR; rs2228570), cytochrome P450 2R1 ( CYP2R1; rs10741657), 7-dehydrocholesterol reductase ( DHCR7; rs12785878), and group-specific component ( GC; rs2282679) to determine whether variants of those alleles influenced total serum 25(OH)D concentrations.

Targeted single molecule sequencing methodology for ovarian hyperstimulation syndrome.

Background: One of the most significant issues surrounding next generation sequencing is the cost and the difficulty assembling short read lengths. Targeted capture enrichment of longer fragments using single molecule sequencing (SMS) is expected to improve both sequence assembly and base-call accuracy but, at present, there are very few examples of successful application of these technologic advances in translational research and clinical testing. We developed a targeted single molecule sequencing (T-SMS) panel for genes implicated in ovarian response to controlled ovarian hyperstimulation (COH) for infertility.

Kinase insert domain receptor/vascular endothelial growth factor receptor 2 (KDR) genetic variation is associated with ovarian hyperstimulation syndrome.

Background: The objective of this investigation was to determine if kinase insert domain/vascular endothelial growth factor receptor 2 (KDR/VEGFR2) genetic variation was associated with the development of ovarian hyperstimulation syndrome (OHSS) in patients undergoing controlled ovarian hyperstimulation (COH).

Methods: This was a case-control study of 174 patients who underwent controlled ovarian stimulation. Patient blood samples were genotyped for single nucleotide polymorphisms (SNPs) spanning the KDR locus.

Status of pharmacy practice experience education programs.

Objective: To assess financial, personnel, and curricular characteristics of US pharmacy practice experiential education programs and follow-up on results of a similar survey conducted in 2001.

Methods: Experiential education directors at 118 accredited US pharmacy colleges and schools were invited to participate in a blinded, Web-based survey in 2011. Aggregate responses were analyzed using descriptive statistics and combined with data obtained from the American Association of Colleges of Pharmacy to assess program demographics, faculty and administrative organizational structure, and financial support.

Out-of-school genomics program for young women demystifies genomics and fosters interest in biomedical sciences.

Background: Pharmacogenomics (PGx) plays a critical role in personalized medicine; however, most healthcare practitioners lack the training and confidence in PGx required to fully utilize its potential. Although continuing education and inclusion of PGx into the professional curricula will begin to address this deficiency, PGx education at the secondary and postsecondary levels would demystify PGx and pique interest at an academic stage that is key to funneling PGx curious students into the science and healthcare pipeline earlier.

Methods: This article describes the development and evaluation of a genomics outreach program targeted at young women in high school with the ultimate goal of recruiting students into an undergraduate PGx program and school of pharmacy.

Engaging the next generation of healthcare professionals in genomics: planning for the future.

There is broad agreement that healthcare professionals require fundamental training in genomics to keep pace with scientific advancement. Strong models that promote effective genomic education, however, are lacking. Furthermore, curricula at many institutions are now straining to adapt to the integration of additional material on next-generation sequencing and the bioethical and legal issues that will accompany clinical genomic testing.

Association between the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) rs4073366 polymorphism and ovarian hyperstimulation syndrome during controlled ovarian hyperstimulation.

Background: The aim of this study was to determine the relationship between a purported luteinizing hormone/chorionic gonadotropin (LHCGR) high function polymorphism (rs4539842/insLQ) and outcome to controlled ovarian hyperstimulation (COH).

Methods: This was a prospective study of 172 patients undergoing COH at the Fertility and IVF Center at GWU. DNA was isolated from blood samples and a region encompassing the insLQ polymorphism was sequenced.

First report of warfarin dose requirements in patients possessing the CYP2C9*12 allele.

Background: Warfarin is the most frequently prescribed anticoagulant in North America and Europe. It is administered as a racemate, but S-warfarin is principally responsible for its anticoagulant activity. Cytochrome P450 (CYP) 2C9 is the enzyme primarily responsible for the metabolism of S-warfarin.

Adjunctive sitagliptin therapy in postoperative cardiac surgery patients: a pilot study.

Aim. We aimed to determine if sitagliptin added to standard postoperative standardized sliding-scale insulin regimens improved blood glucose. Methods.

The current and future state of pharmacogenomics medical education in the USA.

Healthcare professionals (e.g., physicians, physician assistants, pharmacists, nurses and genetic counselors) believe pharmacogenomics (PGx) is essential to personalized medicine; however, they still lack confidence prescribing, dosing, interacting with other healthcare professionals and counseling patients with regard to PGx.

Pharmacogenomics instruction in US and Canadian medical schools: implications for personalized medicine.

Aims: To determine the extent of pharmacogenomics instruction at US and Canadian medical schools, characterize perceptions of curricular coverage, identify curricular resources and compare responses with similar studies conducted in US pharmacy schools and British medical schools.

Materials & Methods: A survey was sent to the pharmacology department chairs of US and Canadian medical schools accredited by the Liaison Committee on Medical Education or the American Osteopathic Association's Commission on Osteopathic College Accreditation. Data were collected from July 2009 to February 2010.

Development of an undergraduate pharmacogenomics curriculum.

Pharmacogenomic biomarkers are becoming increasingly common in medicine and drug development. However, there is a genuine concern that the healthcare workforce will be ill-equipped to translate this information to clinical practice. As a result, a major effort is underway to educate future healthcare professionals on pharmacogenomics.

Frequency of CYP3A4, CYP3A5, CYP2C9, and CYP2C19 variant alleles in patients receiving clopidogrel that experience repeat acute coronary syndrome.

The presence of cytochrome P450 (CYP) variant alleles may reduce the activation of the prodrug clopidogrel to its active state. This research evaluated the frequency of variant alleles in the genes coding for CYP3A4, CYP3A5, CYP2C9, and CYP2C19 enzymes in patients on clopidogrel therapy and experiencing repeat acute coronary syndrome (ACS) compared to a control group with a matching ethnic composition. Real-time polymerase chain reaction was used for allelic discrimination.