PharmGKB PGx summaries now available in the Genetic Testing Registry

The Genetic Testing Registry (GTR) now contains summaries written by PharmGKB Curators regarding the association between genes and drug responses that have CPIC therapeutic recommendations. These can be found on the GTR website under Conditions/Phenotypes and links to relevant clinical tests are provided on each page:

• Warfarin response
• Codeine response
• Clopidogrel response
• Abacavir hypersensitivity 
• Simvastatin response
• Allopurinol response 

Visualizing Levels of Evidence

PharmGKB Clinical Annotations provide a summary of an association between a genetic variant and a drug response. Each is assigned a level of evidence by our curators, based on established criteria.

We have created an illustration to help users understand the 4 levels of evidence:

PharmGKB Clinical Annotations are rated based on the level of evidence for the association 

CPIC guidelines now posted on guidelines.gov

Six CPIC PGx-based dosing guidelines are now available on the National Guideline Clearinghouse website, a public resource for evidence-based clinical guidelines, an initiative of the Agency for Healthcare Research and Quality, US Department of Health Services. 

View the CPIC guidelines on the NGC website: 

• CYP2D6, CYP2C19 & tricyclic antidepressants
• CYP2D6 & codeine
• TPMT & thiopurines
• HLA-B & allopurinol
• HLA-B & abacavir
• SLCO1B1 & simvastatin

Read more about CPIC and view all PGx-based dosing guidelines available on PharmGKB.

"Jack of all trades" drug pathway published

Methylene blue has many clinical uses including the treatment of methemoglobinemia and malaria, as a diagnostic dye and even has potential as a therapy for Alzheimer's disease.

A PharmGKB summary combining the methylene blue pharmacodynamics pathway with the oxidative stress regulatory and pentose phosphate pathways in red blood blood cells has been published in PG&G and is now available to read online.

PharmGKB Methylene Blue Pathway, PD

Together the pathways help explain why people with G6PD deficiency (caused by underlying genetic variants) are more susceptible to drug-induced hemolysis, and why methemoglobinemia treatment with methylene blue is not effective in these individuals.    

Read the article:
PharmGKB summary: methylene blue pathway.

McDonagh EM, Bautista JM, Youngster I, Altman RB, Klein TE.  
Pharmacogenet Genomics. 2013 Sep;23(9):498-508.

Personalized Prescriptions: Russ Altman's TEDx Talk

The mission of PharmGKB and the role of CPIC's therapeutic guidelines are nicely introduced in Russ's TEDxStanford talk, in which he uses the commonly prescribed drug codeine as an example to explain pharmacogenetics.

4 basic lessons are outlined:
1. People don't respond in the same way to drugs.
2. Genetics is behind our response to drugs and these differences.
3. PharmGKB is a resource for this information.
4. Physicians want to use PGx in their practice...CPIC writes evidence-based guidelines to enable this to happen.

• Watch the talk
• For more information on PharmGKB read Whirl-Carrillo et al, 2012
• Learn more about codeine and CYP2D6
• Read the CPIC CYP2D6 genotype-based therapeutic recommendations for codeine

New Pathway for Abacavir

We have posted a new pathway on PharmGKB summarizing the pharmacokinetics, pharmacodynamics and pharmacogenetics of abacavir.

Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) pro-drug, used for treating human immunodeficiency virus (HIV) infection. Abacavir is converted through several enzymatic steps into its active form, carbovir 5’-triphosphate (CBV-TP), which works by blocking the action of HIV reverse transcriptase. Approximately 5-8% of patients experience a hypersensitivity reaction (HSR) within the first 6 weeks of abacavir treatment. These HSRs can be severe and even fatal, particularly if the drug is discontinued then rechallenged. Abacavir HSRs have been strongly linked with the presence of the HLA-B*57:01 allele. For more information on the pharmacogenetics of abacavir, as well as the pharmacokinetics and pharmacodynamics, please view the entire pathway description.

View all pathways on PharmGKB.

Update to CYP2C19 TPP lookup table

We have verified that position rs3758581 in CYP2C19*1 is allele A. The CYP2C19 TPP lookup table has been updated accordingly.

View CYP2C19 haplotypes.