Arthur F Harralson

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. This is due to the inadequate incorporation of PGx content into professional curricula. Compared with other health professions, Doctor of Pharmacy programs have integrated more PGx content. Unlike other healthcare professionals, pharmacists have extensive training in pharmacology, drug selection, drug dosage, drug-drug interactions and are uniquely accessible to patients. We suggest pharmacists are the best poised to facilitate incorporating PGx into therapeutic decision-making. Based on our experience as undergraduate and pharmacy PGx educators, we further reflect on our experience educating future healthcare professionals on PGx.

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. Complete data were obtained for 92 patients enrolled over a 3-month period. There were no significant differences in the presence of the examined CYP3A4, CYP3A5, CYP2C9, or CYP2C19 variant alleles between the two groups. The present data indicate that patients currently receiving clopidogrel therapy who present with repeat ACS do not have higher frequency of the examined variant alleles compared to a control group.

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. This paper describes the development of a year-long course that aims to instill the fundamental concepts of this rapidly growing field into the minds of undergraduate students. This course offers the advantage of exposing students to the concepts of pharmacogenomics prior to their enrollment in PhD, PharmD or MD/DO graduate programs.

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. One-hundred and eighty patients were enrolled, with 40 (22%) being sufficient, 25-hydroxy vitamin D level 25(OH)D ≥ 30 ng/mL, and 140 (78%) being insufficient, 25(OH)D < 30 ng/mL. Of the 4 genes, 2 genes, CYP2R1 (rs10741657) and GC (rs2282679), demonstrated a significant association related to vitamin D status. Subjects with 1 or more variant alleles at rs10741657 were almost 3.7 (odds ratio [OR] 3.67; 95% confidence interval [CI]: 1.35-9.99) times more likely be insufficient in vitamin D and subjects with 1 or more variant alleles at rs2282679 were about half (OR 0.42; 95% CI: 0.18-0.93) as likely to be insufficient in vitamin D. Allelic variations in CYP2R1 (rs10741657) and GC (rs2282679) affect vitamin D levels, but variant alleles on VDR (rs2228570) and DHCR7 (rs12785878) were not correlated with vitamin D deficiency, 25(OH)D < 30 ng/mL.

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. This article advocates for core competencies focused on job function, which will best prepare providers to be end-users of healthcare information. In addition, it argues in favor of online and blended learning models that incorporate student genotyping and specific training in the ethical, legal and social issues raised by genomic testing.

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. PGx knowledge was assessed by pre- and post-tests. Focus groups assessed the impact of the workshop on attitudes toward the clinical utility of PGx. RESULTS Both student knowledge of PGx, and its perceived clinical utility, increased immediately following the workshop. However, exposure to PGx on clinical rotations following the workshop seemed to influence student attitudes toward PGx utility. CONCLUSION Personal CYP2D6 testing improves both knowledge and comfort with PGx. Continued exposure to PGx concepts is important for transfer of learning.

Hypoxia Inducible Factor 1: A Urinary Biomarker of Kidney Disease

Identifying noninvasive biomarkers of kidney disease is valuable for diagnostic and therapeutic purposes. Hypoxia inducible factor 1 (HIF‐1) expression is known to be elevated in the kidneys in several renal disease pathologies. We hypothesized that the urinary HIF‐1a mRNA level may be a suitable biomarker for expression of this protein in chronic kidney disease (CKD). We compared HIF‐1a mRNA levels from urine pellets of CKD and healthy subjects. To ensure that urinary HIF‐1a mRNA is of kidney origin, we examined colocalization of HIF‐1a mRNA with two kidney specific markers in urine cells. We found that HIF‐1a mRNA is readily quantifiable in urine pellets and its expression was significantly higher in CKD patients compared with healthy adults. We also showed that the urinary HIF‐1a mRNA comes primarily from cells of renal origin. Our data suggest that urinary HIF‐1a mRNA is a potential biomarker in CKD and can be noninvasively assessed in patients.

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. A prospective, randomized, double-blind, placebo-controlled pilot study was conducted in diabetic cardiac surgery patients. Patients received sitagliptin or placebo after surgery for 4 days. The primary endpoint was to estimate the effect of adjunctive sitagliptin versus placebo on overall mean blood glucose in the 4-day period after surgery. Results. Sixty-two patients participated. Repeated measures tests indicated no significant difference between the groups in the overall mean blood glucose level with a mean of 147.2 ± 4.8 mg/dL and 153.0 ± 4.6 mg/dL for the test and the control group, respectively (P = 0.388). Conclusions. Sitagliptin added to normal postoperative glucose management practices did not improve overall mean blood glucose control in diabetic patients in the postoperative setting.

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.