CYP2C8 VIP published in PG&G

CYP2C8 is a member of the cytochrome P450 family of drug metabolizing enzymes. It plays a major role in the metabolism of many commonly used drugs. Several CYP2C8 SNPs have been associated with variability in metabolism, disposition and response for drugs such as repaglinide, rosiglitazone, pioglitazone, paclitaxel, bisphosphonates, amiodarone and amodiaquine.  We have recently published the CYP2C8 pharmacogenomic summary in Journal Pharmacogenetics and Genomics.

Find out more...

View our CYP2C8 VIP on PharmGKB.

Read our new publication:
PharmGKBsummary:  very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 8

View all VIPs on PharmGKB.

New PharmGKB VIP Summary: NAT2

N-acetyltransferase enzymes (NAT1 and NAT2) are involved in the metabolism and detoxification of xenobiotics. NAT2 is predominantly expressed in the liver and has a role in the metabolism of numerous therapeutic drugs including caffeine and BiDil. Genetic variants in the NAT2 gene result in a slow, intermediate or rapid acetylator phenotype.

Numerous studies have reported an association between slow acetylator status (based on NAT2 genotype) and anti-TB drug-induced hepatotoxicity, though other studies find no such association. Similarly, the association between NAT2 genetic variants and side effects of co-trimoxazole or hydralazine is also unclear.  

The PharmGKB VIP Summary for NAT2 discusses these contradictions and links to summaries of important NAT2 variants underlying these PGx associations. 

 

Tacrolimus and cyclosporine pathways published

Tacrolimus and cyclosporine are two immunosuppressants given to solid organ transplant patients to prevent allograft rejection. A PharmGKB summary discussing the pharmacokinetics, pharmacodynamics and pharmacogenetics of these two drugs has been published in Pharmacogenetics and Genomics, and is now available to read online ahead of print. The summary also includes two comprehensive pathway diagrams covering the pharmacokinetics and pharmacodynamics of the drugs.

Read the article:
PharmGKB summary: cyclosporine and tacrolimus pathways.
Barbarino JM, Staatz CE, Venkataramanan R, Klein TE, Altman RB
Pharmacogenet Genomics. 2013 Aug 5.

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.