Thursday, October 16, 2014

New pathway: Ibuprofen Pharmacodynamics

We have added a new pathway: ibuprofen PD pathway  to PharmGKB's pathway collections.

Ibuprofen is a traditional non-steroidal anti-inflammatory drug (NSAID) widely used for its analgesic, anti-inflammatory, and anti-pyretic properties. The main mechanism of action of  ibuprofen is the non-selective, reversible inhibition of the cyclooxygenase enzymes COX-1 and COX-2 (encoded by genes PTGS1 and PTGS2, respectively). The ibuprofen PD pathway depicts the mechanisms of action of the drug and highlights genes mediating the diverse biological effects triggered by ibuprofen.

View  ibuprofen PD pathway on PharmGKB.

View all pathways at PharmGKB.

PharmGKB Wikipedia page

PharmGKB now has a Wikipedia page. The page provides an overview of our purpose, as well as the types of content available on the website.

PharmGKB would like to invite the community to add to the page, or email us suggestions for what you think would be useful to include.

Visit our new Wikipedia page at https://en.wikipedia.org/wiki/PharmGKB.

Email us suggestions for expanding our Wikipedia page at feedback@pharmgkb.org.



Wednesday, October 15, 2014

The genetics of warfarin dose: focus on African Americans

Warfarin has a narrow therapeutic window, therefore it is important to get the dosage for a patient correct - too low or too high a dose can have dangerous consequences. However, there is large interindividual variability in dose. Incorporation of a patient's genotypes at the polymorphisms CYP2C9*2 (C>T at rs1799853), CYP2C9*3 (A>C at rs1057910) and VKORC1 (G>A at rs9923231) into a dosing algorithm can help better predict the warfarin dose required by an individual (see the CPIC dosing guideline).

These three variants are rare in African American and African populations, and thus a larger percentage of variability in warfarin dosage remains unexplained in these patients compared to White individuals (see commentary below). There is therefore a need to identify genetic variants found in African Americans and Africans that could be used to enhance prediction of dosage in these patients.

A study in this month's issue of Blood outlines an exome sequencing project in African Americans that revealed a novel variant in the FPGS gene associated with warfarin dose. The G allele of rs7856096 was significantly associated with lower warfarin dose in both the discovery and independent replication cohorts of African American patients. This allele was shown to be most prevalent in populations on the African continent, and found at a frequency of around 0.2 in the discovery and replication cohorts. Adding this variant to the IWPC dosing algorithm helped to explain an additional 3.3% of dose variability in the combined cohort of African Americans. Preliminary functional analysis showed that the G allele may result in reduced FPGS expression. FPGS encodes an enzyme involved in folate homeostasis - though the biological mechanism behind the association with warfarin dose has yet to be investigated, the authors discuss that folate can affect warfarin metabolism and coagulation status.

Read the commentary:
Warfarin pharmacogenetics: it matters if you're black or white
Wadelius M. Blood. 2014 Oct 2;124(14):2171.

Read the article: 
Daneshjou R, Gamazon ER, Burkley B, Cavallari LH, Johnson JA, Klein TE, Limdi N, Hillenmeyer S, Percha B, Karczewski KJ, Langaee T, Patel SR, Bustamante CD, Altman RB, Perera MA. Blood. 2014 Oct 2;124(14):2298-305.

Thursday, October 2, 2014

Gemcitabine pathway published in Pharmacogenetics and Genomics

Gemcitabine is a cancer drug used to treat solid tumors as well as certain blood cancers. It can be administered alone or in combination with other drugs as part of a chemotherapy regimen. The genetic variants hypothesized to play a role in the variability of patient response to gemcitabine as well as those genetic variants that may influence severity of adverse events are summarized.

Click on the picture to view the pathway

Photo of a big bunny rabbit!


Read the publication: PharmGKB summary: gemcitabine pathway

Alvarellos ML, Lamba J, Sangkuhl K, Thorn CF, Wang L, Klein DJ, Altman RB, Klein TE.
Pharmacogenetics and Genomics.  Advanced online publication. 2014 August 26 doi: 10.1097/FPC.0000000000000086




Wednesday, September 24, 2014

SNP-its Study Summaries

The University of Florida Health Personalized Medicine Program has released "SNP-its" study summaries for pharmacogenomic articles with clinical relevance.    The editorial team reviews articles from multiple journals and writes summaries for the ones most relevant to practicing clinicians.  Those interested are welcome to subscribe to a monthly newsletter.  Online, readers can browse summaries by topic

In the first newsletter, SNP-its highlights articles about
They also provide an overview of the personalized medicine program at UF Health.

PharmGKB is pleased to work with the SNP-its initiative to highlight articles with these summaries on our website in the coming weeks.  Look for the SNP-its icon on PharmGKB!

Thursday, September 18, 2014

CPIC PEG interferon-alpha guideline now available on guideline.gov

More CPIC PGx-based dosing guidelines are now available on the National Guideline Clearinghouse (NGC) website.  NGC is a public resource for evidence-based clinical guidelines, an initiative of the Agency for Healthcare Research and Quality, US Department of Health Services.
The most recent CPIC guideline on NGC is:
Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3 (IL28B) genotype and PEG interferon-α–based regimens.

View 10 CPIC guidelines on the NGC website: 

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

Friday, September 5, 2014

New CPIC Guideline: CYP2C9, HLA-B and Phenytoin

Guidelines regarding the use of pharmacogenomic tests for CYP2C9 and HLA-B in dosing phenytoin have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).

Phenytoin is broadly used to treat epilepsy, but it has a narrow therapeutic index and wide inter-patient variability.  Much of this variability is due to genetic variations in CYP2C9 and dosing levels can be altered based on patient genotype.  Additionally, HLA-B*15:02 is associated with an increased risk of phenytoin-induced cutaneous adverse drug reactions, and it is recommended that patients with at least one copy of this variant allele receive an alternate drug.

For details, see the CPIC guideline on PharmGKB.
 
For other CPIC guidelines see the list of CPIC publications and guidelines in progress.