ClinGen is hosting a Clinical Genomics Career Panel webinar series this summer for individuals interested in career in clinical genomics. Sessions are moderated and panel members will discuss their work and career paths. All are welcome to join!
Tuesday, June 21, 2022
PharmGKB Acyclovir/Ganciclovir Pathway Published
The PharmGKB Acyclovir/Ganciclovir Pathway has recently been published in the journal Pharmacogenetics and Genomics.
Acyclovir (ACV) and ganciclovir (GCV) are commonly prescribed antivirals to treat infections caused by herpes viruses, varicella-zoster virus or cytomegalovirus (eg. cold sores, shingles and chicken pox, etc.). The pathway, co-developed by Maud Maillard along with other members of the Yang Lab in St. Jude, as well as members of the PharmGKB team, outlines the metabolism, transport, and mechanism of action of ACV and GCV with a view to decipher the existing interpatient variability, and highlights pharmacogenomics implications by the variants of the NUDT15 and ABCC4 genes on ACV and GCV efficacy. Further work is needed to validate these findings and discover other candidates, with the aim of optimizing antiviral therapy.
View the interactive pathway on PharmGKB:
Acyclovir/Ganciclovir Pathway, Pharmacokinetics/Pharmacodynamics
Read our new publication:
PharmGKB summary: acyclovir/ganciclovir pathway
Maud Maillard, Li Gong, Rina Nishii, Jun J Yang, Michelle Whirl-Carrillo, Teri E Klein
Pharmacogenet Genomics. 2022 Jul 1;32(5):201-208. Epub 2022 May 30.
PMID: 35665708
View all pathways on PharmGKB.
Thursday, June 2, 2022
Expansion of pharmacogenetics education agreed as part of lawsuit settlement
Oregon Health & Science University (OHSU) will introduce new educational initiatives on the risks of prescribing the chemotherapy drug capecitabine to patients with DPD deficiency as part of a lawsuit settlement.
The settlement was reached with Joanne McIntyre, whose husband David died as a result of severe capecitabine toxicity. David carried variations in the gene DPYD, which encodes the DPD enzyme. DPD is involved in metabolism of fluoropyrimidine drugs, including capecitabine. Variants in DPYD, such as those that David carried, can inactivate the DPD enzyme, leading to DPD deficiency. Patients with DPD deficiency are unable to properly metabolize capecitabine and other fluoropyrimidines, and are at risk of experiencing severe drug toxicity. In David's case, this toxicity was fatal.
PharmGKB has annotations of several clinical guidelines for capecitabine and DPYD, including those from CPIC and the DPWG. These guidelines uniformly recommend either a dose reduction or selection of an alternative drug in patients with DPD deficiency.
OHSU will hold seminars to educate clinicians on the risks associated with DPD deficiency, how to identify severe capecitabine toxicity in patients and how to administer the antidote. They will also include a module on the topic in their fellowship program and provide a written resource guide to staff in their oncology department. Going forward, patients identified as candidates for capecitabine chemotherapy will be informed of the risks associated with DPD deficiency and, where appropriate, will be offered testing.
We at PharmGKB applaud Joanne's singular dedication to saving patients' lives and OHSU's commitment to implement these changes. Resources on capecitabine pharmacogenomics, including annotations on clinical guidelines for the use of DPYD genotypes in capecitabine prescribing, can be found at the PharmGKB capecitabine drug page.
Thursday, May 19, 2022
Update to PharmGKB Pediatric Summaries - BPCA Drugs
The latest round of PharmGKB’s pediatric drug summaries is now live on PharmGKB pediatric. This release includes summaries for 55 drugs, bringing the total summary count to over 180, now including all drugs on the Best Pharmaceuticals for Children Act (BPCA) priority list in addition to all CPIC guideline drugs.
- Alfentanil
- Amiodarone
- Ampicillin
- Azithromycin
- Bosentan
- Cidofovir
- Ciprofloxacin
- Clindamycin
- Clonidine
- Dexmedetomidine
- Digoxin
- Doxycycline
- Furosemide
- Granisetron
- Griseofulvin
- Heparin
- Hydralazine
- Hydrochlorothiazide
- Hydromorphone
- Hydroxycobalamin
- Hydroxyurea
- Isotretinoin
- Labetalol
- Levofloxacin
- Levothyroxine
- Lidocaine
- Lisinopril
- Lithium
- Lorazepam
- Lurasidone
- Meropenem
- Metformin
- Methylprednisolone
- Midazolam
- Molindone
- Nafcillin
- Nicardipine
- Nifedipine
- Nifurtimox
- Olanzapine
- Pentobarbital
- Piperacillin-Tazobactam
- Pralidoxime
- Prednisolone
- Sertraline
- Sildenafil
- Spironolactone
- Terbutaline
- Timolol
- Topiramate
- Tranexamic Acid
- Valganciclovir
- Vancomycin
- Vecuronium
Monday, May 16, 2022
Response to the American Academy of Pediatrics' Statement "Eliminating Race-Based Medicine"
Looking forward in research, there is an urgent need to direct research efforts towards underserved populations to address the issues of health disparities. Additionally, clinical implementation of pharmacogenomics needs the development of truly race-agnostic dosing guidelines and algorithms.
Michelle Whirl-Carrillo (Co-Principal Investigator and Director of PharmGKB)
Li Gong
Rachel Huddart
Ingrid Keseler
Clarissa J. Klein
Binglan Li
Caroline F. Thorn
Matt W. Wright (Director, Stanford ClinGen)
Mark Woon
Wednesday, May 4, 2022
Ask a Curator for Healthcare Professionals on June 7th
Sign up here for Tuesday June 7th at 12pm EST, 9am PST, 5pm GMT
Want to be notified about future Ask a Curator events? Join our mailing list here.
Thursday, April 21, 2022
What does *1 really mean? And why does that matter?
A Haiku about PGx for National Poetry Month.
Diagnosed star one,
Yet severe toxicity.
What did the lab test?
What does *1 really mean? And why does that matter?
The star alleles of the drug metabolizing enzyme genes are an unusual way of defining variation and are perhaps one of the most misunderstood aspects of pharmacogenomics. Arising from attempts to describe and standardize the molecular basis of different drug phenotypes; debrisoquine poor metabolizer phenotype, etc [PMID: 7773298, PMID: 8807658]. Sometimes authors use the term “wild type”, even for humans, to describe the most common form of the gene or protein in a given population where it displays the expected drug metabolism phenotype. The *1 allele is generally used to denote the absence of the variants tested. However, it is not a stable assignment; a *1/*1 individual only tested at one locus may not have the same genetic sequence as a *1/*1 individual tested for a panel of 10 variants in the same gene. This really matters when evaluating the likelihood of drug phenotype - the "reference" is only as good as the number of variants that were checked. *1 is rather a placeholder, it is the absence of certainty, because even with a panel that covers variants that represent 99% of known variation (in the populations examined so far which are not representative of the full global population) there may still be rare variants with significant impact on protein function that we may not yet have documented. While a *1/*1 may not be at increased risk of toxicity (or other phenotypes), or require a change of dosage immediately, they still have the baseline level of risk and it shouldn’t be a huge surprise if they exhibit an adverse reaction to a drug.
Recent publications of case studies that concluded a lack of involvement of known pharmacogenes without documenting what was tested:
PMID:35180762 - “Acral Skin Rash Caused by Altered Mercaptopurine
Metabolism in Maintenance Therapy for B-Cell
Acute Lymphoblastic Leukemia” excerpt “TPMT and NUDT15 genotype at diagnosis were wildtype alleles and therefore we started with full 6-MP dosing.”
This issue is not limited to pharmacogenes using star allele nomenclature: “5-Fluorouracil Neurotoxicity in the Absence of Dihydropyrimidine Dehydrogenase Deficiency Case Report” [PMID:35419161] excerpt “Our patient tested negative for DPD mutations, but it remains possible she harbored a genetic variant not accounted for in the genetic testing panel. Other known risk factors include mutations in the orotate phosphoribosyltransferase and thymidylate synthase genes… “
We recommend authors always include the list of all variants that were tested, and other features see [PMID:30406943].
Thursday, April 14, 2022
Update to PharmGKB Pediatric Drug Summaries
The third round of PharmGKB's pediatric drug summaries is now live on PharmGKB pediatric. This release includes over 20 additional drugs with a focus on those on the Best Pharmaceuticals for Children Act (BPCA) priority list, including:
- Albendazole
- Amphotericin b
- Artesunate
- Atropine
- Baclofen
- Benznidazole
- Betamethasone
- Canakinumab
- Cefepime
- Ceftazidime
- Chlorproguanil
- Cortisone acetate
- Dopamine
- Eltrombopag
- Epinephrine
- Etomidate
- Fosfomycin
- Glycopyrrolate
- Montelukast
- Nevirapine
- Ritonavir
Wednesday, April 6, 2022
"Ask a Curator" live zoom event
PharmGKB curators will hold a series of live Q&A events over Zoom to help people find and use different aspects of the knowledgebase. We hope this will be a great way to answer questions about PharmGKB and PGx which are specific to users’ individual needs or projects. These events will demonstrate the full extent of the resources available on PharmGKB, as well as details about those resources and how to download, use, and cite data from PharmGKB.
In order to tailor these events for users with similar needs from PharmGKB, the first event will focus on researchers. Future events geared towards educators and clinicians are in the works, as well as events hosted at different times for our global audience. We will also be recording this upcoming event along with future events for those who are unable to attend live. Recordings will be posted on the PharmGKB YouTube channel.
We are asking people to please register in advance with their questions so curators can better focus these events. There will also be the opportunity to ask questions during the event. Events will be limited to 20 participants to allow enough time for everyone’s questions to be answered.
Sign up here for Tuesday April 26th at 12pm EST, 9am PST, 5pm GMT
Can’t make it but want to sign up for a future Ask a Curator? Join our mailing list here.
Monday, March 21, 2022
National Academy Seeking Public Feedback on Use of Population Descriptors in Genomics Research
The National Academy's Committee on Use of Race, Ethnicity, and Ancestry as Population Descriptors in Genomics Research is now actively requesting public comments from those involved in genomics research about how they use descriptors like race, ethnicity, and ancestry as well as thoughts on potential improvements to usage.
For those who would like to be considered as a potential speaker at their workshop on April 4th, the deadline for submission is March 23rd. Comments will be accepted until June 1st, 2022, and may be potentially considered for a summer workshop or use in the committee's final report.
We encourage PharmGKB and CPIC users to please provide their thoughts, in order to help the committee incorporate feedback from as many people as possible as they continue this important work.
Thursday, February 24, 2022
Retirement of CYP3A5 alleles in PharmVar
The PharmVar CYP3A5 expert panel has undertaken an extensive review of CYP3A5 allelic variation which led to the retirement of three star alleles, namely CYP3A5*2, *4 and *5. Based on new data, their defining variants were always found together with the CYP3A5*3-defining splice defect (c.219-237) meaning that their variants are part of CYP3A5*3 haplotypes and do not occur on their own as previously assumed. Specifically, c.1193C>A (formerly defining CYP3A5*2) is now part of the CYP3A5*3.010 suballele, c.599A>G (formerly defining CYP3A5*4) is now part of the CYP3A5*3.009 suballele, and c.432+2T>C is part of the CYP3A5*3.005 suballele which has first been described in 2003 as published as CYP3A5*3G.
This update makes genotype testing and analysis simpler moving forward. CYP3A5*2, *4 and *5 no longer need to be tested as they are tagged by the CYP3A5*3 variant and thereby accurately identified and reported as CYP3A5*3. Note that in the past, a patient who tested homozygous for c.219-237 (CYP3A5*3) and heterozygous for c.1193C>A (CYP3A5*2) may have been reported as having a CYP3A5*3/*3+*2 diplotype.
This update on CYP3A5 nomenclature is now shown on the PharmVar CYP3A5 page and is described in more detail in the PharmVar CYP3A5 GeneFocus review published in Clinical Pharmacology and Therapeutics.
PharmGKB, CPIC and PharmCAT have been updated accordingly to reflect this change.
Monday, February 21, 2022
Update to individual statin pathways to support release of new CPIC guidelines for statins
To coincide with the release of the updated CPIC guidelines for SLCO1B1, ABCG2 and CYP2C9 and statin-associated musculoskeletal symptoms, we have updated the statin pharmacokinetic (PK) pathways. We now have one PK pathway for each individual drug in the guideline and have added details of the specific metabolites as well as the candidate genes and references.
Atorvastatin Pathway, Pharmacokinetics
Fluvastatin Pathway, Pharmacokinetics
Lovastatin Pathway, Pharmacokinetics
Pitavastatin Pathway, Pharmacokinetics
Pravastatin Pathway, Pharmacokinetics
Rosuvastatin Pathway, Pharmacokinetics
Simvastatin Pathway, Pharmacokinetics
Note: If you have visited pathways recently you may need to refresh your browser or empty cookies to see the updated versions. Plus the history log at the bottom of the pathway lets you know if you are seeing the most updated version.
Friday, February 18, 2022
CPIC Publishes Guideline for SLCO1B1, ABCG2, CYP2C9 and Statin Therapy
- simvastatin, atorvastatin, lovastatin, pravastatin and pitavastatin based on SLCO1B1 phenotype
- rosuvastatin based on SLCO1B1 and ABCG2 phenotypes
- fluvastatin based on SLCO1B1 and CYP2C9 phenotypes
Monday, February 14, 2022
Registration opens for CPIC-PGRN 2022 meeting in Denver, Colorado
We are excited to announce that registration is open for the 2022 CPIC-PGRN meeting: Diversifying PGx Science to Improve Implementation. The meeting will be held at the University of Colorado on May 10th, 11th, and 12th in Denver, CO. Registration, agenda, and hotel information available at the meeting website. Early bird registration is now open and is $250.00. The deadline for early bird registration is April 1, 2022. Regular registration will open April 2, 2022 and is $350.00. The deadline to register is May 1, 2022.
We are keeping an eye on the COVID status and will abide by the restrictions and guidelines set by the University of Colorado at the time of the meeting. We are planning a COVID “rain date” in case we need to reschedule the meeting. If the meeting is cancelled due to COVID, registration fees will be refunded. No virtual option will be available.
The draft agenda can be found on the meeting website. We are still finalizing final titles and speakers and we will post the final agenda once complete.
Participants are invited to submit abstracts for the poster sessions. Please send your abstract to CPIC-PGRN2022@pgrn.org. Acceptance notifications and guidelines will be sent prior to the early registration deadline (April 1st).
Abstract Submission guidelines:
Final Submission Deadline: March 18th, 2022
Required Sections: Authors, Institutions, Background, Methods, Results, Conclusions
1 figure or table may be included
Word limit: 500 words
Please note that submitting an abstract does not register you for this meeting.
Hope to see you there! If you have any questions about registration, please email kelly.caudle@stjude.org.
Best wishes,
Kelly Caudle and Teri Klein (CPIC co-PIs)
Tuesday, February 8, 2022
PharmGKB Heparin-Induced Thrombocytopenia Pathway published
A PharmGKB pathway of heparin-induced thrombocytopenia (HIT) has been published in Pharmacogenetics and Genomics.
Heparin is a commonly used anticoagulant. The pathway, written by Elise Miller along with other members of the Karnes lab at the University of Arizona as well as members of the PharmGKB team, outlines the atypical immune response which can occur in some patients receiving heparin. HIT can have a mortality rate of up to 30% and shares some similarities with COVID-19 while patients with COVID-19 have been found to be at an increased risk of HIT. Pharmacogenomics research has identified some candidate biomarkers, particularly in immune system receptors, which may affect a patient’s risk of experiencing HIT, however further work is needed to validate these and discover other candidates.
An interactive version of the pathway can be found on the PharmGKB website.
Wednesday, January 19, 2022
CPIC Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update
Clopidogrel is a commonly prescribed antiplatelet prodrug and CYP2C19 is a significant contributor in the two-step conversion of clopidogrel to its active metabolite. Response to clopidogrel varies widely and CYP2C19 intermediate and poor metabolizers experience reduced platelet inhibition and increased risk for major adverse cardiac and cerebrovascular events.
The 2022 update includes expanded indications for CYP2C19 genotype-guided antiplatelet therapy, increased strength of recommendation for CYP2C19 intermediate metabolizers, and evidence from an expanded literature review.
For therapeutic recommendations and further details, please refer to the Guideline for Clopidogrel and CYP2C19.