Listen to an interview with the lead author of the CPIC HLA-B - abacavir dosing guideline

In this interview for The Aids Reader, Micheal Martin, PharmD, addresses why doctors may be reluctant to prescribe abacavir to HIV patients due to risk of hypersensitivity reactions, and explains how the genotype-based dosing guidelines recently published by CPIC can help guide therapy and avoid giving the drug to those who are at risk.

Listen to the podcast

View the CPIC guidelines for HLA-B and abacavir

Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype and abacavir dosing. Martin MA, Klein TE, Dong BJ, Pirmohamed M, Haas DW, Kroetz DL. Clin Pharmacol Ther. 2012 Apr;91(4):734-8.

Text-Mining tool revalidated by the PharmGKB Curators

Keeping up with the ever-growing large volume of scientific articles published each day is a challenge, and there is a need for efficient text-mining tools that could support curation of this information.

The PharmGKB Scientific Curators worked with informaticians at the Institute of Computational Linguistics in Switzerland to test and develop a text-mining tool called ODIN (OntoGene Document INspector) that identifies articles with drug-gene relationships. The tool highlights the genes and drugs within the article abstract and enables the user to view the results, and check or modify the entities that have been annotated automatically by the system.

The results of the revalidation study are published in Database:

"Using ODIN for a PharmGKB revalidation experiment"
Fabio Rinaldi, Simon Clematide, Yael Garten, Michelle Whirl-Carrillo, Li Gong, Joan M. Hebert, Katrin Sangkuhl, Caroline F. Thorn, Teri E. Klein, Russ B. Altman. Database, Vol 2012, Article IA bas021, doi: 10.1093/database/bas021
Read the PDF

PharmGKB featured on Stanford's Discovery Walk

The PharmGKB is included on the Stanford University Medical School 'Discovery Walk' monument, alongside major discoveries and achievements in the medical sciences over the last 150 years. On Bench panel 10_13 (located on the Discover Walk outside the Beckman Center), genomics and the post-genomics era are featured. Here the mission of the PharmGKB as a database of how human genetic variation impacts the response to drugs is highlighted by a quote from Russ Altman, stating that "the future of medicine is using the genome to make decisions".

The pharmacogenetic example of the anticoagulant drug warfarin is highlighted with the PharmGKB Warfarin Pathway, Pharmacodynamics, which provides an overview of the genes involved in warfarin action and it's effects in the body.

Find out more...
view genotype-based dosing guidelines for warfarin and information about genetic variants involved in warfarin metabolism and drug effects in the PharmGKB.

Watch the PGx educational video from St Jude's Children's Research Hospital

Protocol investigators and family members of patients from St Jude's Family Advisory Council discuss the PG4KDS pharmacogenetics implementation project in a video - we have added a link to the video on our website under the Outreach tab: "PGEN4Kids Study Information".

In the video, Mary Relling provides an introduction to pharmacogenetics and the PG4KDS project, and then the group discuss important issues including:

• can genetic variants that give information about drug response be separated from those that give information about disease risk?
• why are genetic tests different from other clinical tests? 
• the advantages and disadvantages of placing genetic results in the medical record

View more articles and videos about pharmacogenomics under our Outreach tab.

Clopidogrel: indication-specific pharmacogenetics

An article published in the May edition of Clinical Pharmacology & Therapeutics reviews the mixed results seen in different studies for the association between adverse cardiovascular events and the CYP2C19*2 allele in patients taking clopidogrel.

The CYP2C19*2 allele confers loss of function of the CYP2C19 enzyme and thus poor metabolism of clopidogrel (view the role of CYP2C19 in the PharmGKB Clopidogrel Pharmacokinetics Pathway). Poor metabolism of clopidogrel results in less active metabolite and thus reduced inhibition of platelet aggregation - this is associated with an increased risk of blood clot formation, which can lead to adverse cardiovascular events.

The review concludes that the evidence supports an association between high risk for adverse cardiovascular events in patients with the CYP2C19*2 allele who are prescribed clopidogrel following percutaneous coronary intervention (PCI), and genotyping in these cases should be used to guide therapy, but not for other indications.

Read the article:

Clopidogrel: a case for indication-specific pharmacogenetics. 
Johnson JA, Roden DM, Lesko LJ, Ashley E, Klein TE, Shuldiner AR.
Clin Pharmacol Ther. 2012 May;91(5):774-6.

How Do I Subscribe to the PharmGKB Blog?

There are several ways to view our blog:

 

1.   Click on the rotating box images on our homepage - these link directly to the related blog post for each news item.

2. Click on our "News & Events" tab on the top blue bar on our website. Here you can also see the PharmGKB twitter feed and PGx in the news.

3. Go directly to the PharmGKB blog: pharmgkb.blogspot.com

 and to keep updated with new blog posts...

 

1. Click on the RSS feed icon at the bottom of our homepage

              or the RSS feed icon on pharmgkb.blogspot.com

2. Add your email address to the FOLLOW BY EMAIL box on pharmgkb.blogspot.com to get updates by email.

The PharmGKB Knowledge Pyramid

Figure 1: The PharmGKB Knowledge Pyramid. A visual representation of the
information available at PharmGKB and the research by the PharmGKB team.

The PharmGKB Knowledge Pyramid (Figure 1) provides users with a visualization of the different types of information found in our knowledge base and, how this information is acquired and integrated together – from the accumulation of gene-drug knowledge at the bottom of the pyramid, to the implementation of pharmacogenomics in the clinic at the top. Each step of the pyramid is described here on our website under the Overview tab.

The Clinical Pharmacogenetics Implementation Consortium (CPIC)

The Clinical Pharmacogenetics Implementation Consortium (CPIC) was established in order to provide drug-dosing guidelines based on an individual’s genotype, if this genetic information is already available. These guidelines are published in Clinical Pharmacology and Therapeutics and summaries of the guidelines can be viewed in the PharmGKB on drug or gene pages.

Find out more about CPIC, and the CPIC gene-drug pairs.

Data-driven prediction of drug effects and interactions

Tatonetti, et al. have recently published a database of off-label side effects (named OFFSIDES) and a database of drug-drug interactions (named TWOSIDES), both using data derived from the FDA Adverse Event Reporting Systems (AERS).

Using these databases, and validating results in patient Electronic Medical Records, they found an increased risk of prolonged QT interval (after a heartbeat there is a delay in the repolarisation of the heart) when patients were cotreated with both serotonin reuptake inhibitors (SSRIs, antidepressants) and thiazides (diuretics), compared to patients treated with either drug alone. Prolonged QT has been linked to an increased risk of arrhythmias and sudden death. These findings may have importance in the prediction, monitoring or prevention of adverse effects caused by drug-drug interactions.

Data-driven prediction of drug effects and interactions.

Tatonetti NP, Ye PP, Daneshjou R, Altman RB. Sci Transl Med. 2012 Mar 14;4(125):125ra31.

Download the databases: OFFSIDES and TWOSIDES

Browse the FDA Adverse Event Reporting System.

Welcome to our newly designed website

Here's some of the things we've changed:

1. The rotating box displaying news and important information - we will be updating this regularly so keep an eye out!
2. We have added a "Download Data" button now on the homepage for convenience
   
3. "Curators' Favorite Papers" button on the homepage
   
4. About Us
   This is found on the top bar on each page of our website. Here you can learn about the mission of the PharmGKB and meet our team.
5. News and Events
   This is found on the top bar on each page of our website. Here you will find up-to-date PharmGKB news such as pharmacogenetics news, information about recent PharmGKB publications and upcoming meetings the PharmGKB will be attending.
6. Projects
   This is found on the top bar on each page of our website. Here you will find information about our consortia groups, collaborations and research projects.
7. Publications
   This is found in the top right hand corner of every page on our website. Here you will find an up-to-date list of PharmGKB publications, including CPIC guidelines, VIP summaries and Pathways.
8. Social media
   Keep up-to-date with the latest PharmGKB news, updates and publications. You can follow us on:
   
   

If you were familiar with our old site, here are some tips to guide you through the new design...

Variation in our genes could increase the risk of kidney damage when treated with an anti-HIV drug

Tenofovir is an anti-HIV drug that works by inhibiting the replication of the HIV virus. Transporter genes encode proteins that are involved in the movement of the drug in and out of cells in the body, and the eventual elimination of the drug from the body. Clearance and elimination of a drug is important to avoid build up of a drug, which can lead to toxicity. Variations within several transporter genes (including ABCC4 and ABCC10) have been associated with an increased risk of kidney damage in patients who are treated with tenofovir. The genetic variants may have an effect on the protein’s function or expression, and alter the clearance of the drug from the kidneys – this could result in the accumulation of the drug in the kidneys, causing toxicity.

To find out more about the transport and effects of Tenofovir, see our newly updated Tenofovir/ Adefovir Pharmacokinetics Pathway.

Go to our Tenofovir drug page to view associations with specific gene variants and further pharmacogenetic-related information.