Analytical validation of a laboratory-development multigene pharmacogenetic assay

Rosas-Alonso, Rocío; Queiruga, Javier; Arias, Pedro; Monte, Álvaro Del; Yuste, Fernando; Rodriguez-Antolín, Carlos; Losantos-García, Itsaso; Borobia, Alberto M.; Rodrı́guez-Nóvoa, Sonia

doi:10.1097/fpc.0000000000000438

Cited by 4 publications

(3 citation statements)

References 37 publications

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“…Each TaqMan™ SNP assay contains two allele-specific probes and a primer pair to detect the specific SNP target (analyzed SNPs can be found in Supplementary Table S1 ). The validation study conducted for this technology was previously published [ 52 ].…”

Section: Methodsmentioning

confidence: 99%

Prognostic Impact of Dihydropyrimidine Dehydrogenase Germline Variants in Unresectable Non-Small Cell Lung Cancer Patients Treated with Platin-Based Chemotherapy

Guijarro-Eguinoa,

Arjona-Hernandez,

Stewart

et al. 2023

IJMS

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Platin-based chemotherapy is the standard treatment for patients with non-small cell lung cancer (NSCLC). However, resistance to this therapy is a major obstacle in successful treatment. In this study, we aimed to investigate the impact of several pharmacogenetic variants in patients with unresectable NSCLC treated with platin-based chemotherapy. Our results showed that DPYD variant carriers had significantly shorter progression-free survival and overall survival compared to DPYD wild-type patients, whereas DPD deficiency was not associated with a higher incidence of high-grade toxicity. For the first time, our study provides evidence that DPYD gene variants are associated with resistance to platin-based chemotherapy in NSCLC patients. Although further studies are needed to confirm these findings and explore the underlying mechanisms of this association, our results suggest that genetic testing of DPYD variants may be useful for identifying patients at a higher risk of platin-based chemotherapy resistance and might be helpful in guiding future personalized treatment strategies in NSCLC patients.

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Section: Methodsmentioning

confidence: 99%

Prognostic Impact of Dihydropyrimidine Dehydrogenase Germline Variants in Unresectable Non-Small Cell Lung Cancer Patients Treated with Platin-Based Chemotherapy

Guijarro-Eguinoa,

Arjona-Hernandez,

Stewart

et al. 2023

IJMS

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“…Each TaqMan ™ SNV assay contains two allelespecific probes and a primer pair to detect the specific SNV target. The validation study conducted for this technology was previously published (Rosas-Alonso et al, 2021). For each PGx test available in our lab, predefined SNVs were analyzed (Supplementary Table S1).…”

Section: Pharmacogenetic Testing Methodologymentioning

confidence: 99%

Advancing pharmacogenetic testing in a tertiary hospital: a retrospective analysis after 10 years of activity

Stewart,

Dodero-Anillo,

Guijarro-Eguinoa

et al. 2023

Front. Pharmacol.

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The field of pharmacogenetics (PGx) holds great promise in advancing personalized medicine by adapting treatments based on individual genetic profiles. Despite its benefits, there are still economic, ethical and institutional barriers that hinder its implementation in our healthcare environment. A retrospective analysis approach of anonymized data sourced from electronic health records was performed, encompassing a diverse patient population and evaluating key parameters such as prescribing patterns and test results, to assess the impact of pharmacogenetic testing. A head-to-head comparison with previously published activity results within the same pharmacogenetic laboratory was also conducted to contrast the progress made after 10 years. The analysis revealed significant utilization of pharmacogenetic testing in daily clinical practice, with 1,145 pharmacogenetic tests performed over a 1-year period and showing a 35% growth rate increase over time. Of the 17 different medical departments that sought PGx tests, the Oncology department accounted for the highest number, representing 58.47% of all genotyped patients. A total of 1,000 PGx tests were requested for individuals susceptible to receive a dose modification based on genotype, and 76 individuals received a genotype-guided dose adjustment. This study presents a comprehensive descriptive analysis of real-world data obtained from a public tertiary hospital laboratory specialized in pharmacogenetic testing, and presents data that strongly endorse the integration of pharmacogenetic testing into everyday clinical practice.

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“…The difference in clinical outcomes across different patients may be caused by their unique personal genetic polymorphisms that influence the metabolism of the drugs [4][5][6][7]. Potentially relevant candidate genes and theirs impact of response variability have been actively studied for the antiplatelet agents, but none more so than clopidogrel [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Associations of CYP2C19 and F2R genetic polymorphisms with platelet reactivity in Chinese ischemic stroke patients receiving clopidogrel therapy

Zhang

Zhu

et al. 2021

Pharmacogenetics and Genomics

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Objectives Genetic variation has been considered a major contributor to the high variability in the response to dual antiplatelet therapy in patients with acute ischemic stroke or transient ischemic attack. Recently, incidences of ischemic stroke are increasing rapidly in China. We aimed to evaluate the influence of potential determinants on the response of antiplatelet therapy and adverse events in Chinese ischemic stroke patients receiving clopidogrel-aspirin treatment. Methods Based on the clopidogrel drug response pathway and the coagulation and anticoagulation function, we systematically selected 34 genetic polymorphisms in 12 candidate genes. Three hundred and eight patients were divided into 2 groups according to their degree of inhibition of platelet aggregation. Multivariate analysis was then performed to assess the influence of demographic, clinical and genetic factors on platelet reactivity in Chinese ischemic stroke patients. Results We found that polymorphisms in CYP2C19 and F2R genes were still significantly associated with platelet reactivity in Chinese ischemic stroke patients (P = 0.037 and 0.015). The newly identified rs168753 in F2R gene may influence the efficacy to clopidogrel-aspirin therapy for ischemic stroke patients. We also found that ischemic stroke patients with low level of inhibition of platelet aggregation had higher risk of recurrent ischemic events (P = 0.001). Conclusions Together, these results emphasized the necessity of genotype-directed antiplatelet therapy and facilitated to minimize adverse ischemic events.

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Analytical validation of a laboratory-development multigene pharmacogenetic assay

Cited by 4 publications

References 37 publications

Prognostic Impact of Dihydropyrimidine Dehydrogenase Germline Variants in Unresectable Non-Small Cell Lung Cancer Patients Treated with Platin-Based Chemotherapy

Prognostic Impact of Dihydropyrimidine Dehydrogenase Germline Variants in Unresectable Non-Small Cell Lung Cancer Patients Treated with Platin-Based Chemotherapy

Advancing pharmacogenetic testing in a tertiary hospital: a retrospective analysis after 10 years of activity

Associations of CYP2C19 and F2R genetic polymorphisms with platelet reactivity in Chinese ischemic stroke patients receiving clopidogrel therapy

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