New VIP Summary for CYP2C8

A new VIP summary is available for CYP2C8, a member of the cytochrome P450 family of drug metabolizing enzymes. CYP2C8 accounts for 7% of CYP content in the liver, and is expressed to a lesser extent in the kidney, adrenal gland, mammary gland, brain, ovary, uterus, and duodenum.  CYP2C8 plays a major role in the metabolism of many commonly used drugs [Article:15900280]. Several CYP2C8 SNPs have functional consequences [Article: 20459297] and have been associated with variability in CYP2C8-mediated metabolism and altered disposition and response for many commonly used drugs such as repaglinide, rosiglitazone, pioglitazone,paclitaxel, bisphosphonates, amiodarone and amodiaquine [Articles:12429347, 11668219, 17361129, 23536207, 11767116, 12530467, 18769365]. As a result, CYP2C8 has emerged as a significant pharmacogene. 

For more information on this VIP gene and its variants see the VIP tab for CYP2C8.

For all VIP gene summaries on pharmgkb, see here.

CPIC guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 Update

The 2013 update of the CPIC guidelines for CYP2C19 and clopidogrel dosing is now available online, as an accepted article preview.

This updated guideline refines the recommendations for specific CYP2C19 alleles, with emphasis on the appropriate indication for CYP2C19 genotype-directed antiplatelet therapy, and, an expanded literature review to include recent published evidence.

Read the accepted article preview version:

Clinical PharmacogeneticsImplementation Consortium (CPIC) guidelines for cytochrome P450-2C19 (CYP2C19)genotype and clopidogrel therapy: 2013 Update.

Scott SA, Sangkuhl K, Stein CM, Hulot JS, Mega JL, Roden DM, Klein TE, Sabatine MS, Johnson JA, Shuldiner AR.

Clin Pharmacol Ther. 2013 May 22. doi: 10.1038/clpt.2013.105. [Epub ahead of print]

See excerpts from the guideline update:

Please click here to see excerpts from the guideline update and access downloads of the updated and original article and supplements. 

Please click here for a complete list of CPIC publications.

Big Data in Biomedicine

PharmGKB Developers and Curators attended the Big Data in Biomedicine conference this week, organized by Stanford University and the University of Oxford. The talks and panels raised a plethora of issues surrounding storing, sharing, analyzing, validating, visualizing and utilizing Big Data for improving healthcare and to drive change. Among the challenges is the need to integrate multiple big data sources together (genomic, metabolome, transcriptome, medical records, behavioural, environmental). Empowering patients, reproducible statistical analyses, and bioinformatics education were also discussed.

New name for IL28B gene = IFNL3

PharmGKB has updated our gene names that comply with The Human Genome Nomenclature Committee (HGNC) approved symbol, approved name, and synonyms.

One particular name change we would like to highlight with this update:
The HGNC-approved gene symbol for IL28B is now IFNL3 (interferon lambda 3) - a gene with variants that are associated with response to peginterferon alfa-2a, alfa-2b and ribavirin.

IFNL3 PGx information:

• FDA and EMA drug labels
• Level 1 Clinical Annotations
• Genetic tests
• Variant annotations

View the full IFN gene family in HGNC.

Curators' Favorite Papers

The current Curators' Favorite Papers' highlights the higher frequency of genetic variants conferring increased risk for adverse drug reactions (ADRs) for many commonly used drugs in persons of African descent. Differences in drug response, cure rates and survival outcomes between different ethnic populations exist. To assess this, Aminkeng et al. genotyped 1330 individuals of African and European descent over 4,000 SNPs in 350 key drug absorption, distribution, metabolism, elimination and toxicity genes. Publicly available databases including PharmGKB were utilized to prioritize the selection of functional SNPs. The distribution of many variants were significantly different between African and European populations. These results were presented in the context of clinical annotations (toxicity, efficacy, ADR and drug response pathway) that were curated from PharmGKB and published studies. Important differences among the African populations were also observed in the frequency of variants. Results presented in this paper may translate to significant differences in drug efficacy and safety profiles in different populations.