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Pharmacological Research Feb 2024The development of Pharmacogenetics and Pharmacogenomics in Western Europe is highly relevant in the worldwide scenario. Despite the usually low institutional support,...
The development of Pharmacogenetics and Pharmacogenomics in Western Europe is highly relevant in the worldwide scenario. Despite the usually low institutional support, many research groups, composed of basic and clinical researchers, have been actively working for decades in this field. Their contributions made an international impact and paved the way for further studies and pharmacogenomics implementation in clinical practice. In this manuscript, that makes part of the Special Issue entitled Spanish Pharmacology, we present an analysis of the state of the art of Pharmacogenetics and Pharmacogenomics research in Europe, we compare it with the developments in Spain, and we summarize the most salient contributions since 1988 to the present, as well as recent developments in the clinical application of pharmacogenomics knowledge. Finally, we present some considerations on how we could improve translation to clinical practice in this specific scenario.
Topics: Pharmacogenetics; Precision Medicine; Europe
PubMed: 38199278
DOI: 10.1016/j.phrs.2024.107061 -
The Journal of Molecular Diagnostics :... Mar 2022Clinical laboratories offering genome sequencing have the opportunity to return pharmacogenomic findings to patients, providing the added benefit of preemptive testing...
Clinical laboratories offering genome sequencing have the opportunity to return pharmacogenomic findings to patients, providing the added benefit of preemptive testing that could help inform medication selection or dosing throughout the lifespan. Implementation of pharmacogenomic reporting must address several challenges, including inherent limitations in short-read genome sequencing methods, gene and variant selection, standardization of genotype and phenotype nomenclature, and choice of guidelines and drugs to report. An automated pipeline, lmPGX, was developed as an end-to-end solution that produces two versions of a pharmacogenomic report, presenting either Clinical Pharmacogenetics Implementation Consortium or US Food and Drug Administration guidelines for 12 genes. The pipeline was validated for performance using reference samples and pharmacogenetic data from the Genetic Testing Reference Materials Coordination Program. To determine performance and limitations, lmPGX was compared with three additional publicly available pharmacogenomic pipelines. The lmPGX pipeline offers clinical laboratories an opportunity for seamless integration of pharmacogenomic results with genome reporting.
Topics: Genetic Testing; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing; Phenotype
PubMed: 35041930
DOI: 10.1016/j.jmoldx.2021.12.001 -
Pharmacogenomics Jun 2021Pharmacogenetic testing is available to healthcare professionals to guide drug selection and prevent adverse events. However, its implementation in the clinical practice... (Review)
Review
Pharmacogenetic testing is available to healthcare professionals to guide drug selection and prevent adverse events. However, its implementation in the clinical practice of psychiatry/neurology still has barriers, mainly due to a lack of evidence. We conducted a literature search on Cochrane Library, Embase and Pubmed, from their inception to 18 June 2020. We included 16 published systematic reviews. The most studied drug categories were anticonvulsants and selective serotonin reuptake inhibitors associated with human leukocyte antigen and cytochrome P450 genes (, , , , ), classified as critically low quality/low quality. There is a need for more robust studies with adequate design to assess the potential benefits of adopting pharmacogenetics in health systems and services.
Topics: Anticonvulsants; Cytochrome P-450 Enzyme System; Humans; Neurology; Pharmacogenetics; Pharmacogenomic Testing; Psychiatry; Selective Serotonin Reuptake Inhibitors
PubMed: 33973477
DOI: 10.2217/pgs-2020-0187 -
International Journal of Medical... 2023Metformin is the most often prescribed drug for people with type 2 diabetes (T2D). More than 120 million patients with T2D use metformin worldwide. However, monotherapy... (Review)
Review
Metformin is the most often prescribed drug for people with type 2 diabetes (T2D). More than 120 million patients with T2D use metformin worldwide. However, monotherapy fails to achieve glycemic control in a third of the treated patients. Genetics contribute to some of the inter-individual variations in glycemic response to metformin. Numerous pharmacogenetic studies have demonstrated that variations in genes related to pharmacokinetics and pharmacodynamics of metformin's encoding transporters are mainly associated with metformin response. The goal of this review is to evaluate the current state of metformin pharmacogenetics and metabolomics research, discuss the clinical and scientific issues that need to be resolved in order to increase our knowledge of patient response variability to metformin, and how to improve patient outcomes. Metformin's hydrophilic nature and absorption as well as its action mechanism and effectiveness on T2D initiation are discussed. The impacts of variations associated with various genes are analysed to identify and evaluate the effect of genetic polymorphisms on the therapeutic activity of metformin. The metabolic pattern of T2D and metformin is also indicated. This is to emphasise that studies of pharmacogenetics and metabolomics could expand our knowledge of metformin response in T2D.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Metabolomics; Metformin; Pharmacogenetics
PubMed: 36619226
DOI: 10.7150/ijms.77206 -
Journal of Clinical Pharmacology Apr 2022Race and ethnicity can contribute to differences in drug exposure and/or response. Here, we report that about 10% of the new molecular entities (NMEs) approved between... (Review)
Review
Race and ethnicity can contribute to differences in drug exposure and/or response. Here, we report that about 10% of the new molecular entities (NMEs) approved between 2014 and 2019 by the US Food and Drug Administration's Center for Drug Evaluation and Research showed differences in exposure and/or response based on race/ethnicity or pharmacogenetic factors known to vary in frequency across global populations. Fewer NMEs (10%) reported differences in the labeling in 2014 to 2019 when compared to about 21% of NMEs approved between 2008 and 2013 that had differences in pharmacokinetics, safety, response, and/or pharmacogenetics. Understanding the underlying mechanisms that lead to such differences and adequate enrollment of racial and ethnic subgroups is essential to obtain sufficient information on exposure and response. Though drug development is global, when heterogeneous populations are not adequately enrolled, the risk-benefit assessments can remain incomplete for certain subgroups. Consequently, this can result in regional differences in drug approval, population-specific prescribing recommendations, or need for additional postmarketing studies to address concerns related to exposure, response, or lack of representation that lead to gaps in information.
Topics: Drug Approval; Drug Development; Ethnicity; Humans; Pharmaceutical Preparations; Pharmacogenetics; United States; United States Food and Drug Administration
PubMed: 34608640
DOI: 10.1002/jcph.1978 -
Pharmacogenomics Aug 2019The Nigerian population exhibits huge ethnic and genetic diversity, typical of African populations, which can be harnessed for improved drug-response and disease... (Review)
Review
The Nigerian population exhibits huge ethnic and genetic diversity, typical of African populations, which can be harnessed for improved drug-response and disease management. Existing data on genes relevant to drug response, so far generated for the population, indeed confirm the prevalence of some clinically significant pharmacogenes. These reports detail prevailing genetic alleles and metabolic phenotypes of vital drug metabolizing monooxygenases, transferases and drug transporters. While the utilization of existing pharmacogenomic data for healthcare delivery remains unpopular, several past and on-going studies suggest that a future shift toward genotype-stratified dosing of drugs and disease management in the population is imminent. This review discusses the present state of pharmacogenomics in Nigeria and the potential benefits of sustained research in this field for the population.
Topics: Alleles; Animals; Ethnicity; Genetic Variation; Genotype; Humans; Nigeria; Pharmacogenetics; Phenotype
PubMed: 31453771
DOI: 10.2217/pgs-2019-0046 -
Journal of Clinical Oncology : Official... Aug 2023
Topics: Humans; Pharmacogenomic Testing; Informed Consent; Pharmacogenetics; Genetic Testing
PubMed: 37267582
DOI: 10.1200/JCO.23.00664 -
Cancer Treatment Reviews Jan 2024The development of immune checkpoint inhibitors (ICIs) has a tremendous effect on the treatment options for multiple types of cancer. Nonetheless, there is a large... (Review)
Review
The development of immune checkpoint inhibitors (ICIs) has a tremendous effect on the treatment options for multiple types of cancer. Nonetheless, there is a large interpatient variability in response, survival, and the development of immune-related adverse events (irAEs). Pharmacogenetics is the general term for germline genetic variations, which may cause the observed interindividual differences in response or toxicity to treatment. These genetic variations can either be single-nucleotide polymorphisms (SNPs) or structural variants, such as gene deletions, amplifications or rearrangements. For ICIs, pharmacogenetic variation in the human leukocyte antigen molecules has also been studied with regard to treatment outcome. This review presents a summary of the literature regarding the pharmacogenetics of ICI treatment, discusses the most important known genetic variations and offers recommendations on the application of pharmacogenetics for ICI treatment.
Topics: Humans; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Pharmacogenetics; Neoplasms
PubMed: 38043396
DOI: 10.1016/j.ctrv.2023.102662 -
Seminars in Hematology Jul 2020Inherited genetic variations may alter drug sensitivity in patients with acute lymphoblastic leukemia, predisposing to adverse treatment side effects. In this review, we... (Review)
Review
Inherited genetic variations may alter drug sensitivity in patients with acute lymphoblastic leukemia, predisposing to adverse treatment side effects. In this review, we discuss evidence from children and young adults with acute lymphoblastic leukemia to review the available pharmacogenomic data with an emphasis on clinically actionable and emerging discoveries, for example, genetic variants in thiopurine methyltransferase and NUDT15 that alter 6-mercaptopurine dosing. We also highlight the need for ongoing pharmacogenomic research to validate the significance of recent findings. Further research in young adults, as well as with novel therapeutics, is needed to provide optimal therapy in future trials.
Topics: Humans; Pharmacogenetics; Precision Medicine; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 33256902
DOI: 10.1053/j.seminhematol.2020.10.001 -
Pharmacogenomics Jul 2021Several healthcare organizations across Minnesota have developed formal pharmacogenomic (PGx) clinical programs to increase drug safety and effectiveness. Healthcare... (Review)
Review
Several healthcare organizations across Minnesota have developed formal pharmacogenomic (PGx) clinical programs to increase drug safety and effectiveness. Healthcare professional and student education is strong and there are multiple opportunities in the state for learners to gain workforce skills and develop advanced competency in PGx. Implementation planning is occurring at several organizations and others have incorporated structured utilization of PGx into routine workflows. Laboratory-based and translational PGx research in Minnesota has driven important discoveries in several therapeutic areas. This article reviews the state of PGx activities in Minnesota including educational programs, research, national consortia involvement, technology, clinical implementation and utilization and reimbursement, and outlines the challenges and opportunities in equitable implementation of these advances.
Topics: Biomedical Research; Education, Pharmacy, Graduate; Health Personnel; Humans; Minnesota; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 34137665
DOI: 10.2217/pgs-2021-0058