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Genes May 2024Over the last few decades, the implementation of pharmacogenomics (PGx) in clinical practice has improved tailored drug prescriptions [...].
Over the last few decades, the implementation of pharmacogenomics (PGx) in clinical practice has improved tailored drug prescriptions [...].
Topics: Pharmacogenetics; Humans; Precision Medicine
PubMed: 38927650
DOI: 10.3390/genes15060714 -
Current Oncology Reports Apr 2018The goal of this review is to summarize current understanding of pharmacogenetics and pharmacogenomics in chemotherapy-induced cardiotoxicity. (Review)
Review
PURPOSE OF REVIEW
The goal of this review is to summarize current understanding of pharmacogenetics and pharmacogenomics in chemotherapy-induced cardiotoxicity.
RECENT FINDINGS
Most of the studies rely on in vitro cytotoxic assays. There have been several smaller scale candidate gene approaches and a handful of genome-wide studies linking genetic variation to susceptibility to chemotherapy-induced cardiotoxicity. Currently, pharmacogenomic testing of all childhood cancer patients with an indication for doxorubicin or daunorubicin therapy for RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 variants is recommended. There is no recommendation regarding testing in adults. There is clear evidence pointing to the role of pharmacogenetics and pharmacogenomics in cardiotoxicity susceptibility to chemotherapeutic agents. Larger scale studies are needed to further identify susceptibility markers and to develop pharmacogenomics-based risk profiling to improve quality of life and life expectancy in cancer survivors.
Topics: Animals; Antineoplastic Agents; Cardiotoxicity; Daunorubicin; Doxorubicin; Genetic Testing; Humans; Mice; Pharmacogenetics; Polymorphism, Single Nucleotide; Receptors, Retinoic Acid; Retinoic Acid Receptor gamma
PubMed: 29713898
DOI: 10.1007/s11912-018-0696-8 -
Clinical Pharmacology and Therapeutics Sep 2021Clinical annotations are one of the most popular resources available on the Pharmacogenomics Knowledgebase (PharmGKB). Each clinical annotation summarizes the...
Clinical annotations are one of the most popular resources available on the Pharmacogenomics Knowledgebase (PharmGKB). Each clinical annotation summarizes the association between variant-drug pairs, shows relevant findings from the curated literature, and is assigned a level of evidence (LOE) to indicate the strength of support for that association. Evidence from the pharmacogenomic literature is curated into PharmGKB as variant annotations, which can be used to create new clinical annotations or added to existing clinical annotations. This means that the same clinical annotation can be worked on by multiple curators over time. As more evidence is curated into PharmGKB, the task of maintaining consistency when assessing all the available evidence and assigning an LOE becomes increasingly difficult. To remedy this, a scoring system has been developed to automate LOE assignment to clinical annotations. Variant annotations are scored according to certain attributes, including study size, reported P value, and whether the variant annotation supports or fails to find an association. Clinical guidelines or US Food and Drug Administration (FDA)-approved drug labels which give variant-specific prescribing guidance are also scored. The scores of all annotations attached to a clinical annotation are summed together to give a total score for the clinical annotation, which is used to calculate an LOE. Overall, the system increases transparency, consistency, and reproducibility in LOE assignment to clinical annotations. In combination with increased standardization of how clinical annotations are written, use of this scoring system helps to ensure that PharmGKB clinical annotations continue to be a robust source of pharmacogenomic information.
Topics: Databases, Genetic; Drug Labeling; Drug Prescriptions; Humans; Knowledge Bases; Pharmacogenetics; Precision Medicine; Prescription Drugs; Reproducibility of Results
PubMed: 34216021
DOI: 10.1002/cpt.2350 -
Clinical Pharmacology and Therapeutics Aug 2019
Topics: Biotransformation; Clinical Decision-Making; Drug Resistance; Drug-Related Side Effects and Adverse Reactions; Genetic Testing; Humans; Medication Therapy Management; Pharmacogenetics; Pharmacogenomic Variants; Precision Medicine; Reproducibility of Results
PubMed: 31355458
DOI: 10.1002/cpt.1511 -
British Journal of Clinical Pharmacology Jan 2022Pharmacogenomics is increasingly moving into mainstream clinical practice. Careful consideration must be paid to inclusion of diverse populations in research,... (Review)
Review
Pharmacogenomics is increasingly moving into mainstream clinical practice. Careful consideration must be paid to inclusion of diverse populations in research, translation and implementation, in the historical and social context of population stratification, to ensure that this leads to improvements in healthcare for all rather than increased health disparities. This review takes a broad and critical approach to the current role of diversity in pharmacogenomics and addresses potential pitfalls in order to raise awareness for prescribers. It also emphasizes evidence gaps and suggests approaches that may minimize negative consequences and promote health equality.
Topics: Health Promotion; Humans; Pharmacogenetics
PubMed: 34251046
DOI: 10.1111/bcp.14983 -
JAMA Network Open Oct 2023Limited evidence supports multigenetic pharmacogenomics-guided treatment (MPGT) in schizophrenia. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Limited evidence supports multigenetic pharmacogenomics-guided treatment (MPGT) in schizophrenia.
OBJECTIVE
To evaluate the clinical effectiveness of MPGT in schizophrenia in a randomized clinical trial (RCT).
DESIGN, SETTING, AND PARTICIPANTS
This RCT was conducted from March 2020 to March 2022. Male Chinese Han inpatients aged 18 to 60 years diagnosed with schizophrenia with a Positive and Negative Symptom Scale (PANSS) score of 60 or more from 2 selected study hospitals were included. Patients and raters were masked to MPGT or treatment as usual (TAU) randomization.
INTERVENTIONS
Participants were randomly assigned in a 1:1 ratio to receive either MPGT or TAU for 12 weeks.
MAIN OUTCOMES AND MEASURES
The primary efficacy outcome was the percentage change in PANSS total scores (range, 30 to 210) from baseline to week 6 analyzed by a modified intention-to-treat mixed model for repeated measures. The secondary outcome included response and symptomatic remission rates.
RESULTS
A total of 210 participants (mean [SD] age, 29.2 [8.8] years) were enrolled and analyzed, with 113 assigned to MPGT and 97 to TAU. Compared with those randomized to TAU, participants randomized to MPGT demonstrated a significantly higher percentage change in PANSS score (74.2% vs 64.9%; adjusted mean difference, 9.2 percentage points; 95% CI, 4.4-14.1 percentage points; P < .001) and a higher response rate (93 of 113 [82.3%] vs 63 of 97 [64.9%]; adjusted odds ratio, 2.48; 95% CI, 1.28-4.80; P = .01) at the end of week 6.
CONCLUSIONS AND RELEVANCE
In this RCT of MPGT, MPGT was more effective than TAU in treating patients with schizophrenia. These findings suggest that multigenetic pharmacogenomic testing could serve as an effective tool to guide the treatment of schizophrenia.
TRIAL REGISTRATION
Chinese Clinical Trial Registry Identifier: ChiCTR2000029671.
Topics: Male; Humans; Adult; Pharmacogenetics; Schizophrenia; Treatment Outcome
PubMed: 37801319
DOI: 10.1001/jamanetworkopen.2023.35518 -
Molecular Genetics & Genomic Medicine May 2018Perceptions and challenges connecting Pharmacogenomics taught in classrooms and translationing it to advance pharmacy practice rotations and healthcare settings and...
Perceptions and challenges connecting Pharmacogenomics taught in classrooms and translationing it to advance pharmacy practice rotations and healthcare settings and potential areas of development.
Topics: Attitude of Health Personnel; Curriculum; Education, Pharmacy; Humans; Pharmaceutical Services; Pharmacogenetics; Pharmacy; Students, Pharmacy; Surveys and Questionnaires
PubMed: 29852540
DOI: 10.1002/mgg3.417 -
Genes Jan 2024The flavoenzyme N-ribosyldihydronicotinamide (NRH):quinone oxidoreductase 2 (NQO2) catalyzes two-electron reductions of quinones. NQO2 contributes to the metabolism of... (Review)
Review
The flavoenzyme N-ribosyldihydronicotinamide (NRH):quinone oxidoreductase 2 (NQO2) catalyzes two-electron reductions of quinones. NQO2 contributes to the metabolism of biogenic and xenobiotic quinones, including a wide range of antitumor drugs, with both toxifying and detoxifying functions. Moreover, NQO2 activity can be inhibited by several compounds, including drugs and phytochemicals such as flavonoids. NQO2 may play important roles that go beyond quinone metabolism and include the regulation of oxidative stress, inflammation, and autophagy, with implications in carcinogenesis and neurodegeneration. is a highly polymorphic gene with several allelic variants, including insertions (I), deletions (D) and single-nucleotide (SNP) polymorphisms located mainly in the promoter, but also in other regulatory regions and exons. This is the first systematic review of the literature reporting on NQO2 gene variants as risk factors in degenerative diseases or drug adverse effects. In particular, hypomorphic 29 bp I alleles have been linked to breast and other solid cancer susceptibility as well as to interindividual variability in response to chemotherapy. On the other hand, hypermorphic polymorphisms were associated with Parkinson's and Alzheimer's disease. The I and D promoter variants and other NQO2 polymorphisms may impact cognitive decline, alcoholism and toxicity of several nervous system drugs. Future studies are required to fill several gaps in NQO2 research.
Topics: Benzoquinones; Oxidoreductases; Pharmacogenetics; Quinone Reductases; Humans
PubMed: 38254976
DOI: 10.3390/genes15010087 -
Current Protocols Jul 2021Cardiovascular pharmacogenomics is the study and identification of genomic markers that are associated with variability in cardiovascular drug response, cardiovascular...
Cardiovascular pharmacogenomics is the study and identification of genomic markers that are associated with variability in cardiovascular drug response, cardiovascular drug-related outcomes, or cardiovascular drug-related adverse events. This overview presents an introduction and historical background to cardiovascular pharmacogenomics, and a protocol for designing a cardiovascular pharmacogenomics study. Important considerations are also included for constructing a cardiovascular pharmacogenomics phenotype, designing the replication or validation strategy, common statistical approaches, and how to put the results in context with the cardiovascular drug or cardiovascular disease under investigation. © 2021 Wiley Periodicals LLC. Basic Protocol: Designing a cardiovascular pharmacogenomics study.
Topics: Cardiovascular Agents; Cardiovascular Diseases; Humans; Pharmacogenetics; Pharmacogenomic Testing; Phenotype
PubMed: 34232575
DOI: 10.1002/cpz1.189 -
Genes Dec 2020The continuous development of new genotyping technologies requires awareness of their potential advantages and limitations concerning utility for pharmacogenomics (PGx).... (Review)
Review
The continuous development of new genotyping technologies requires awareness of their potential advantages and limitations concerning utility for pharmacogenomics (PGx). In this review, we provide an overview of technologies that can be applied in PGx research and clinical practice. Most commonly used are single nucleotide variant (SNV) panels which contain a pre-selected panel of genetic variants. SNV panels offer a short turnaround time and straightforward interpretation, making them suitable for clinical practice. However, they are limited in their ability to assess rare and structural variants. Next-generation sequencing (NGS) and long-read sequencing are promising technologies for the field of PGx research. Both NGS and long-read sequencing often provide more data and more options with regard to deciphering structural and rare variants compared to SNV panels-in particular, in regard to the number of variants that can be identified, as well as the option for haplotype phasing. Nonetheless, while useful for research, not all sequencing data can be applied to clinical practice yet. Ultimately, selecting the right technology is not a matter of fact but a matter of choosing the right technique for the right problem.
Topics: Haplotypes; High-Throughput Nucleotide Sequencing; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Precision Medicine
PubMed: 33291630
DOI: 10.3390/genes11121456