Monday, October 8, 2018

PharmGKB oxycodone pathway published in Pharmacogenetics and Genomics

The PharmGKB Oxycodone Pathway, Pharmacokinetics is featured on the cover of the October 2018 issue of Pharmacogenetics and Genomics. Oxycodone is an opioid analgesic metabolized by CYP2D6 and CYP3A4/5 to a number of metabolites, including oxymorphone which itself can be used as an analgesic.

The pathway was produced by scientific curator Dr. Rachel Huddart in collaboration with Dr. Melissa Clarke of the Medical Home Development Group and Whole Genome Science Foundation. It discusses the current state of knowledge of both the pharmacokinetics and pharmacodynamics of oxycodone as well as pharmacogenetic research into the drug. Oxycodone is covered by a DPWG guideline, an annotated version of which can be found on the PharmGKB website. You can access the Oxycodone Pathway, Pharmacokinetics on the PharmGKB website here.

Thursday, October 4, 2018

CPIC grant awarded

The co-PIs of the Clinical Pharmacogenetics Implementation Consortium (CPIC), Drs. Mary Relling of St. Jude Children's Research Hospital (SJCRH) and Teri Klein of Stanford University, will receive $5 million over the next 5 years from the National Institutes of Health (NIH) to continue and expand the project.  CPIC was created in 2009 as a partnership between the Pharmacogenomics Research Network (PGRN) and PharmGKB to provide peer-reviewed, evidence-based genotype-directed drug prescribing guidelines for clinicians.  The new funding will enable CPIC to continue its mission to create and update guideline publications and supporting materials to enable translation of pharmacogenomics into the clinic and electronic health care records.  For more information, see the announcement from SJCRH.

Monday, October 1, 2018

Curators' Favorite Papers

An article in Pharmacogenomics Journal puts the spotlight on the need to continue look for candidate genes and variants in many populations even when it seems as though current candidates explain a large amount of variability.  [PMID: 30100615] identifies new candidate genes and variants that are important when the most well known variants are not present.

Rosuvastatin is a HMG-CoA reductase (HMGCR) inhibitor or statin, used in the treatment of high cholesterol and heart disease. The pharmacokinetics of individual statin drugs are influenced by their hydrophobicity, with the more hydrophobic statins being highly dependent on transporters for transport in and out of cells. Rosuvastatin is a hydrophobic statin and undergoes minimal metbolism with around 80% of drug dose excreted unchanged in feces [PMID: 14693307]. The transporter variants SLCO1B1 c.521T>C (rs4149056 p. Val174Ala) and ABCG2 c.421C>A (rs2231142, p. Gln141Lys) are key candidates in rosuvastatin PGx [PMID:16198652][PMID: 25630984]. Soko et al demonstrate that these variants differ in frequency in a range of African populations and are absent in some. They studied rosuvastatin PK in a group of individuals of Bantu decent and identified new variants in the SLCO1B1 and ABCG2 transporters and additional variants in other transporter genes  and regulatory genes that influence transporter expression. PharmGKB will be updating our rosuvastatin PK pathway to include these new genes and variants.

Friday, September 14, 2018

CYP2D6 genotype to phenotype standardization project - seeking feedback

The assignment of the CYP2D6 metabolizer phenotype based on a subject's genotype is an important aspect of clinical implementation of pharmacogenetics knowledge. Especially for CYP2D6, the genotype-inferred phenotypes vary across laboratories and guidelines. The goal of the CYP2D6 genotype to phenotype standardization project is to harmonize this translation. 

The following consensus was reached by a group of CYP2D6 excepts through a series of surveys:
1) Activity score of 1 should be assigned as CYP2D6 intermediate metabolizer
2) Downgrading the CYP2D6*10 allele from activity score 0.5 to 0.25

We are seeking feedback on the final CYP2D6 genotype to phenotype table, which summaries all CYP2D6 metabolizers assignment based on activity score. 

Information about the project are available here Please email any comments to by September 27th.

Tuesday, August 28, 2018

NHGRI/NCI survey on genomics education

The National Human Genome Research Institute (NHGRI), who are supportive of PharmGKB and CPIC, have teamed up with the National Cancer Institute (NCI) to survey research and healthcare professionals about genomics education. The results of this survey will help to determine the resource and training priorities for future genomics education.

PharmGKB and CPIC are both actively working on pharmacogenomic education initiatives and we encourage everyone working in pharmacogenomics to complete the survey. This will highlight the importance of pharmacogenomics in future genomics education.

The survey takes approximately 10 minutes to complete and is tailored to different roles in both research and healthcare. The questions aim to evaluate respondents’ knowledge of genomics and learning needs. It will also help to identify barriers to accessing genomics education as well as preferred training methods.

The survey is open now and can be accessed at until September 15. All responses are anonymous and the results will be presented at the NHGRI meeting on September 25-26.

Friday, August 24, 2018

PharmGKB Demo at U-PGx Summer School

PharmGKB recently held a demonstration of the PharmGKB website as part of the U-PGx Summer School in Bonn, Germany. Scientists, clinicians and pharmacists attending the summer school heard from Dr. Rachel Huddart, one of our Scientific Curators, and were introduced to the various types of information found on the PharmGKB website; from Dosing Guidelines to Pathways and Clinical Annotations. Information from PharmGKB formed an important of the participants’ project work later on in the summer school.

The U-PGx summer school group sees PharmGKB in action

This was a remote demonstration, with Rachel presenting at the summer school online from our Stanford offices. If you are interested in including a demonstration of the PharmGKB website at your pharmacogenomics event, please get in touch with us at