Monday, October 12, 2015

PharmGKB succinylcholine PK/PD pathway published in Pharmacogenetics and Genomics

Succinylcholine (SCH) is a depolarizing neuromuscular blocking agent with a rapid onset of action and short half-life. SCH is commonly used in medical procedures requiring short-term skeletal muscle paralysis, such as intubation during surgery, or emergency medical procedures. The “PharmGKB summary: succinylcholine pathway, PK/PD” has been published in Pharmacogenetics and Genomics. The pathway summary describes the pharmacokinetic and pharmacodynamic pathways of SCH, and adverse reactions to SCH that are associated with variants in the genes BCHE, RYR1, and CACNA1S, as well as in patients with diagnosed with Duchenne or Becker muscular dystrophy. 

View the interactive online version of the pathway here.

See all pathways on PharmGKB.

Saturday, October 10, 2015

Successful implementation of widespread pharmacogenetic testing discussed this week in The Atlantic

An article this week in The Atlantic presents the story of widespread testing for HLA genotypes in some Southeast Asian countries. Simple pharmacogenetic ID cards are issued to inform physicians of a patient’s risk for developing Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) hypersensitivity reactions if prescribed carbamazepine, allopurinol, abacavir, and other drugs. Despite a drop in the incidence of SJS as a result of the cards, better integration with electronic medical records is needed if cases are to be eliminated entirely.

This type of translation of pharmacogenetic research to improve patient outcomes is the goal of the PharmacogenomicsResearch Network (PGRN), supported by the NIH since 2000 under the leadership of Dr. Rochelle Long. Specific PGRN groups address questions ranging from basic science to clinical trials and implementation. In 2009, the Clinical Pharmacogenomics Implementation Consortium (CPIC), led by Dr. Mary Relling of St. Jude Children’s Research Hospital and Dr. Teri Klein of PharmGKB, was established to develop guidelines for and to address barriers to implementation of pharmacogenetic research. The CPIC guidelines for testing of HLA variants in relation to carbamazepine (HLA-B*15:02), allopurinol (HLA-B*58:01), and abacavir (HLA-B:57:01) treatment were published in Clinical Pharmacology and Therapeutics. Each guideline summarizes the relationship of specific HLA variants with hypersensitivity reactions to each drug and recommendations of how to alter care in response. All CPIC guidelines are freely available to the public.

Friday, October 9, 2015

July/August SNPits Summary

The July/August issue of UF Health Personalized Medicine Program's e-newsletter, SNPits, reviews a recent article in the Journal of the American Medical Informatics Association focused on genomic information in the electronic health record (EHR).  The authors of the study looked at how EHRs currently display genomic and genetic information, and how to optimize and improve upon it.  They concluded that the way that genomic information is stored and displayed affects the usefulness of the information, and made several recommendations, including development of clinical decision support (CDS) for genetic results.  Read more.

Wednesday, October 7, 2015

PharmGKB welcomes Alie Fohner to the team

We are pleased to welcome scientific curator Alison (Alie) Fohner to the PharmGKB team. Alie recently earned her PhD in Public Health Genetics at the University of Washington, where she worked with the Pharmacogenomics Research Network group that focuses on rural and underserved populations. Her dissertation included an analysis of genetic and environmental drivers of variation in cytochrome P450 expression in Alaska Native people, and a recommendation for reconciling conflicting ethical and statistical demands in conducting research with historically marginalized populations.  She is excited to be starting with PharmGKB, 10 years after attending a lecture by Russ Altman that inspired her interest in pharmacogenetics, and to be back at Stanford, where she received both a BS and MS in Biology.

Tuesday, October 6, 2015

New CPIC Guideline- UGT1A1 and atazanavir

Guidelines regarding the use of pharmacogenetic tests of UGT1A1 for atazanavir prescribing decisions have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).

Atazanavir is an antiretroviral protease inhibitor administered to patients infected with the human immunodeficiency virus (HIV). Atazanavir, often co-administered with low-dose ritonavir (atazanavir/r), specifically inhibits UGT1A1-mediated glucoronidation of bilirubin, leading to elevations in concentrations of plasma indirect bilirubin (hyperbilirubinemia). The resulting hyperbilirubinemia is not indicative of hepatic injury, but may result in jaundice in patients with genetic variants that negatively impact UGT1A1 function. Patient stigma due to jaundice may be of particular concern to individuals whose line of work requires them to interact frequently with the public, and may also cause individuals with visible jaundice to prematurely discontinue atazanavir. 

In the newly published guidelines, CPIC recommends advising patients with two decreased function UGT1A1 alleles about their increased chances of developing jaundice if prescribed atazanavir/r. The CPIC recommendations suggest that clinicians avoid prescribing atazanavir to such individuals, unless a patient does not consider jaundice to be a concern, or unless a strong argument exists in favor of prescribing atazanavir.  For patients carrying one, or no decreased function UGT1A1 alleles, CPIC deems the likelihood of bilirubin-related discontinuation of atazanavir to be low, and very low, respectively. 

For details, see the CPIC guideline on PharmGKB.

Tuesday, September 22, 2015

Very Important Pharmacogene: RYR1

The new Very Important Pharmacogene (VIP) Summary of RYR1 describes important pharmacogenetic associations as well as disease associations with variants in RYR1. RYR1 encodes a single sub-unit of the ryanodine receptor isoform 1 (RYR1), the predominant ryanodine receptor isoform of skeletal muscle. RYR1 is a calcium channel of the sarcoplasmic reticulum of muscle cells (and endoplasmic reticulum in non-muscle cells) and is critical to excitation-contraction coupling, the process by which an electrical signal is translated into a muscle contraction. RYR1 is the primary locus for malignant hyperthermia susceptibility (MHS), a potentially fatal pharmacogenetic condition triggered by volatile anesthetics, alone or in combination with a depolarizing neuromuscular blocking agent, such as succinylcholine. There is limited evidence that variants in RYR1 may also be associated with statin-induced myopathies. The VIP summary also discusses how advances in sequencing have improved MHS diagnoses in otherwise healthy individuals. 

Read the VIP summary below:

Saturday, September 19, 2015

Precision Medicine Initiative Working Group Releases Report

The Precision Medicine Initiative (PMI) Working Group of the Advisory Committee to the (NIH) Director (ACD) has recently presented a detailed report to the ACD with recommendations on how to a build and manage a diverse research cohort of 1 million people for the PMI. The report discusses a framework for policies affecting patient recruitment, specimen collection and storage, technology infrastructure, operations, privacy, security and sharing of data between researchers and cohort participants. A notable recommendation is the use of arrays that prioritize the inclusion of known pharmacogenetic variants.  The report also recommends including anyone who is willing to participate in the PMI, and emphasizes the importance of having a diverse cohort that is representative of the general population of the United States.The ACD unanimously agreed to accept the PMI Working Group’s report, and according to Dr. Russ Altman, a member of the ACD, "Direct participation is clearly the alternative in this age of consumer empowerment.” 

Read more about the PMI Working Group’s report, including an interview with Dr. Russ Altman with GenomeWeb below: