Saturday, November 21, 2015

Article on PGx by Dean Julie A. Johnson in The Conversation

Dean Julie A. Johnson, Dean of the College of Pharmacy, Distinguished Professor of Pharmacy and Medicine, and Director of the University of Florida Health Personalized Medicine Program at University of Florida published an article in The Conversation on November 20th, 2015 providing an overview of pharmacogenetics. Within the article, Dean Johnson explains the meaning of pharmacogenetics, and then provides two clinically relevant examples of pharmacogenetic associations.

The first example involving treatment of childhood leukemia is the TPMT gene and a class of chemotherapy drugs known as thiopurines. Dean Johnson notes that individuals whose TPMT enzyme does not work properly are given one-tenth the normal dosage of thiopurines, as recommended in guidelines published by the Clinical Pharmacogenetics Implementation Consortium (CPIC). These patients carry two copies of a non-functional TPMT allele, such as *2 or *3A, and are at a 100% risk of developing life-threatening myelosuppression if they receive a normal dose of thiopurines. CPIC also recommends thrice weekly as opposed to daily dosing of thiopurines for these patients, and recommends a dose reduction of 30-50% in individuals who carry one non-functional TPMT allele.

The second example is focused on the CYP2C19 gene and clopidogrel therapy. The CYP2C19 enzyme is the major enzyme responsible for the biotransformation of clopidogrel into its active metabolite. Approximately 25-30% of individuals have a CYP2C19 enzyme with reduced function due to the presence of CYP2C19 alleles such as *2 or *3. These individuals cannot fully convert clopidgrel to its active form, resulting in reduced efficacy of the drug. Dean Johnson cites the CPIC recommendations for clopidogrel, which suggest using an alternative drug in patients who carry CYP2C19 reduced function alleles. She also notes that a study undertaken at the University of Florida showed that when these types of patients were given an alternative drug, they had significantly fewer heart attacks and strokes, and were less likely to die as compared to patients who continued taking clopidogrel.

PharmGKB worked in partnership with the University of Florida Health Personalized Medicine Program on the implementation of pharmacogenetics in medicine, specifically on the creation of a customized genotyping panel for use within their personalized medicine program.

Read the article:

The Conversation - How your genes influence what medicines are right for you

The CPIC guidelines for thiopurine and clopidogrel therapy are available online at PharmGKB

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Read the CPIC guidelines for thiopurine dosing and clopidogrel therapy:

Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, Stein CM, Carrillo M, Evans WE, Klein TE; Clinical Pharmacogenetics Implementation Consortium. Clin Pharmacol Ther. 2011 Dec;90(6):894. PMID: 21270794

Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-219 (CYP2C19) genotype and clopidogrel therapy. Scott SA, Sangkuhl K, Gardner EE, Stein CM, Hulot JS, Johnson JA, Roden DM, Klein TE, Shuldiner AR; Clinical Pharmacogenetics Implementation Consortium. Clin Pharmacol Ther. 2011 Aug;90(2):328-32. PMID: 21716271




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