Wednesday, May 22, 2019

PharmGKB ondansetron and tropisetron pathways published in Pharmacogenetics and Genomics

The PharmGKB pathways for ondansetron and tropisetron have been published in the June 2019 issue of Pharmacogenetics and Genomics. Ondansetron and tropisetron are serotonin receptor antagonists which are prescribed for their antiemetic activity. After an overview of the pharmacokinetics and pharmacodynamics of each drug, the publication discusses the current pharmacogenetic evidence available, some of which has informed the CPIC guidelines for ondansetron and tropisetron.

You can access interactive versions of the Ondansetron Pathway, Pharmacokinetics/Pharmacodynamics and the Tropisetron Pathway,Pharmacokinetics/Pharmacodynamics at the PharmGKB website.

Monday, May 20, 2019

PharmVar core alleles to be used by PharmGKB and CPIC

PharmVar has released core alleles - single, rule-based definitions per star allele distilled from the respective suballeles - for the cytochrome P450 genes CYP2C9CYP2C19, and CYP2D6. Only sequence variations that change an amino acid or impact function by changing expression levels or interfere with splicing and are present in ALL suballeles within a star allele, are part of the core allele definition. Read more about the core alleles in the PharmVar STANDARDS document and in each gene's "READ ME" document. 

Furthermore, part of the latest PharmVar release was the reassignment of CYP2C19*27 to CYP2C19*1.006.

The PharmGKB/CPIC allele definition tables are updated to reflect the core alleles for CYP2C9, CYP2C19, and CYP2D6 and the CYP2C19*27 change.

The PharmGKB/CPIC allele definition files include a “core alleles + overlap” view which reflects the existence of variants in some, but not all, suballeles of a star allele (therefore not part of the core allele) which are also part of core alleles of other star alleles. 

See the following examples.

CYP2D6 100C>T (P34S) is part of some but not all CYP2D6*4 suballeles. Therefore, it is not present in the CYP2D6*4 core allele. However, 100 C>T is part of core allele definitions of a number of CYP2D6 star alleles such as CYP2D6*10.
To reflect the ambiguous presence of 100C>T in the *4 core allele, the variant is represented as a “R” using IUPAC nucleotide code. "R" reflects that either a “G” or “A” (positive strand) can be present at the 100C>T position in *4.

A similar example is 12802G>A (R150H) in CYP2C19. The variant is present in the CYP2C19*11 core allele but also in one of the CYP2C19*2 suballeles. Therefore, 12802G>A is represented as a “R” in the CYP2C19*2 core allele.

This overlap of variants between alleles is visualized in gray (G) in PharmVar’s Comparative Allele ViewEr (CAVE) tool (accessible through the ‘Compare View’ on the gene page), which was released on PharmVar together with the core alleles (see gene "READ ME" documents for more information).

Friday, May 17, 2019

Pharmacogenomics for dermatologists

An introduction to pharmacogenomics in dermatology has been published in Seminars in Cutaneous Medicine and Surgery by Stanford Medicine dermatology resident Dr. Roxana Daneshjou, PharmGKB curator Dr. Rachel Huddart and PharmGKB co-PIs Dr. Teri Klein and Dr. Russ Altman.

After introducing the field of pharmacogenomics, the paper highlights some of the features of PharmGKB, including our search functionality, curated pathways and drug label annotations. The work of CPIC is also introduced with examples of dermatology-relevant guidelines such as carbamazepine and HLA-A/HLA-B. The article concludes with a discussion of the current state of pharmacogenomics implementation in the clinic.

Although the article has a focus on dermatology, it is relevant to anyone who wants to learn more about pharmacogenomic resources and implementation, regardless of their clinical field. The paper can be accessed here.

Tuesday, May 14, 2019

Pharmacogenomics in the clinic

In 2018, Stanford Medicine launched a pilot project, Humanwide, using precision health approaches to predict, prevent and treat disease based on the individual patient in primary care. Over the past year, the Humanwide project provided care to a diverse group of 50 patients based on their individual factors, from lifestyle to DNA data. In addition to disease screening, the patients also underwent pharmacogenomic screening and patients with unusual drug responses received consultation from the Stanford Pharmacogenomics Clinic, led by Dr. Russ Altman.

In this video, Dr. Altman gives an introduction to pharmacogenomics and explains to the patients how their genetic information can be used to guide prescribing decisions to lower the side effects and improve the efficacy of the drugs they are using now and in the future.

“If we can bring pharmacogenomics to the frontlines of medicine, I think we have a better chance of managing health instead of disease," said Dr. Altman. "This is where Precision Health is a powerful idea, where we’re trying to keep people out of the system by giving them the minimum medication at the right time and not having their disease progress, get worse and become chronic diseases”.

To learn more about Stanford Pharmacogenomics Clinic:

To learn more about Stanford Precision Health Initiative: