Advancing Precision Medicine Through the New Pharmacogenomics Global Research Network

Giacomini, Kathleen M.; Karnes, Jason H.; Crews, Kristine R.; Monte, Andrew A.; Murphy, William A.; Oni‐Orisan, Akinyemi; Ramsey, Laura B.; Yang, Jun J.; Whirl‐Carrillo, Michelle

doi:10.1002/cpt.2340

Cited by 7 publications

(2 citation statements)

References 10 publications

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“…Gene-drug pairs with genetics-based prescribing guidelines are already being used in adults to guide current treatment (reactive testing) or to guide future treatment decisions (pre-emptive testing) (Whirl-Carrillo et al, 2012;Abdullah-Koolmees et al, 2020). Organizations such as the Clinical Pharmacogenetics Implementation Consortium (CPIC; https://cpicpgx.org/) (Relling and Klein, 2011;Relling et al, 2020), the Dutch Pharmacogenetics Working Group (DPWG) established by the Royal Dutch Pharmacist's Association (KNMP; https://www.knmp.nl/) (Swen et al, 2008;Swen et al, 2011), the Pharmacogenomics Research Network (Shuldiner et al, 2013;Giacomini et al, 2021), and Ubiquitous Pharmacogenomics (Manson et al, 2017) have released easily accessible public guidelines for implementing pharmacogenetics in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Practice of CYP450 genotyping and phenotyping in children in a real-life setting

et al. 2023

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Pharmacokinetics varies widely between children. Many factors play an important role in this variability, such as ontogeny, pharmacogenetics, gender, comorbidities, and drug-drug interactions. Significant work has already been done in adults to understand the impact of genetic polymorphisms on drug-metabolizing enzyme activity and drug response. Data remain poor in children due to ontogeny that impacts genotyping-phenotyping correlation and the difficulty enrolling children in prospective studies. Our study aimed to describe the use of cytochromes P450 (CYP) phenotyping and/or genotyping tests in children in a real-life setting and assess the correlation between the genotype and the phenotype. We reviewed the results of tests performed between January 2005 and December 2020. Fifty-two children were genotyped and/or phenotyped. Four patients were excluded from the present analysis as they only underwent ABCB1 genotyping, without CYP testing. Of the remainder, 18 underwent simultaneous CYP genotyping and phenotyping, while 17 underwent CYP genotyping only, and 13 underwent CYP phenotyping only. In all cases, investigations were performed after the following situations: insufficient clinical response to treatment, low plasma concentrations, and adverse drug reactions (ADR). The vast majority of cases were related to immunosuppressive or antipsychotic therapy. Genotyping and/or phenotyping explained or contributed to the aforementioned clinical events in 56% of cases. The correlation between the genotype and the phenotype showed variability depending on the assessed cytochrome. In several cases, the phenotype did not correspond to the genotype because of comedications. In conclusion, there is clearly value in guiding drug based on CYP activity in children.

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Section: Discussionmentioning

confidence: 99%

Practice of CYP450 genotyping and phenotyping in children in a real-life setting

et al. 2023

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“…ADRs are a serious clinical problem, with 2.2 million ADRs annually (100,000 of which lead to fatal consequences), and they have a direct medical cost of 200 billion US dollars in the United States (US) [2]. Although big PGx initiatives have demonstrated PGx's utility in the clinical setting [3][4][5][6] and the cost-effectiveness of PGx testing has also been established [7], mostly, PGx diagnostic is implemented in a reactive way, testing only those genes related with the drug which is going to be prescribed. However, pre-emptive PGx testing by a single test covering a sufficient number of medications and future medication exposure may be easier to implement and more cost-effective than reactive PGx testing.…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Analysis of 21 Actionable Pharmacogenes in the Spanish Population: From Genetic Characterisation to Clinical Impact

et al. 2023

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The implementation of pharmacogenetics (PGx) is a main milestones of precision medicine nowadays in order to achieve safer and more effective therapies. Nevertheless, the implementation of PGx diagnostics is extremely slow and unequal worldwide, in part due to a lack of ethnic PGx information. We analysed genetic data from 3006 Spanish individuals obtained by different high-throughput (HT) techniques. Allele frequencies were determined in our population for the main 21 actionable PGx genes associated with therapeutical changes. We found that 98% of the Spanish population harbours at least one allele associated with a therapeutical change and, thus, there would be a need for a therapeutical change in a mean of 3.31 of the 64 associated drugs. We also identified 326 putative deleterious variants that were not previously related with PGx in 18 out of the 21 main PGx genes evaluated and a total of 7122 putative deleterious variants for the 1045 PGx genes described. Additionally, we performed a comparison of the main HT diagnostic techniques, revealing that after whole genome sequencing, genotyping with the PGx HT array is the most suitable solution for PGx diagnostics. Finally, all this information was integrated in the Collaborative Spanish Variant Server to be available to and updated by the scientific community.

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Pharmacogenomics in cancer supportive care: key issues and future directions

Patel

Olver

Ashbury

2021

Support Care Cancer

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Advancing Precision Medicine Through the New Pharmacogenomics Global Research Network

Cited by 7 publications

References 10 publications

Practice of CYP450 genotyping and phenotyping in children in a real-life setting

Practice of CYP450 genotyping and phenotyping in children in a real-life setting

A Comprehensive Analysis of 21 Actionable Pharmacogenes in the Spanish Population: From Genetic Characterisation to Clinical Impact

Pharmacogenomics in cancer supportive care: key issues and future directions

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