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Pharmacogenomics Aug 2023Metformin, a hypoglycemic drug for Type 2 diabetes mellitus, shows variability in pharmacokinetics and response due to membrane transporters. This study followed 34 Type...
Metformin, a hypoglycemic drug for Type 2 diabetes mellitus, shows variability in pharmacokinetics and response due to membrane transporters. This study followed 34 Type 2 diabetes mellitus patients on metformin treatment. Genetic variants in 11 metformin transport-related genes were analyzed, revealing associations. Specifically, rs2289669 A/A and rs1050152 T/T genotypes correlated with glycated hemoglobin values at 6 months. rs2289669 G/A genotype influenced glucose levels at 6 months, while rs3889348 A/A, rs2289669 A/A, rs1050152 C/T and rs12943590 A/A genotypes were linked to glucose levels at 12 months. Additionally, rs2032582 C/A and rs2231137 C/T genotypes impacted cholesterol levels at 12 months. These findings shed light on metformin response determinants, offering insights for further research.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Pharmacogenetics; Organic Cation Transport Proteins; Polymorphism, Single Nucleotide; Hypoglycemic Agents; Glucose
PubMed: 37610884
DOI: 10.2217/pgs-2023-0109 -
Currents in Pharmacy Teaching & Learning Mar 2024Clinical pharmacogenomics is an expanding area in healthcare that relies heavily on pharmacists for advocacy and implementation. To support pharmacists' significant... (Review)
Review
BACKGROUND
Clinical pharmacogenomics is an expanding area in healthcare that relies heavily on pharmacists for advocacy and implementation. To support pharmacists' significant roles in clinical pharmacogenomics, pharmacy schools and colleges in the United States (US) have strived to incorporate pharmacogenomics education into their curricula, and various teaching strategies have been employed in recent years to meet pharmacogenomics educational outcomes. The six major strategies reported in the literature are described and compared in this review, which culminates in a proposed longitudinal curriculum design for pharmacogenomics education.
METHODS
Publications focused on pharmacogenomics education to pharmacy students within the US in the past decade were evaluated and summarized.
RESULTS
The major education strategies that have been studied are didactic lecture, personal genotyping or personal genomic testing, simulation laboratory activity, interprofessional education, practice-based activity such as clinical rotation, and combinational courses. Strengths and limitations of each teaching strategy are summarized and discussed.
IMPLICATIONS
Based upon each education strategy's strengths and weaknesses, the authors propose a longitudinal curriculum design to ensure that pharmacogenomics is taught multiple times to pharmacy students with diverse formats and teaching objectives conducive to long-term knowledge retention and practice readiness. Through this longitudinal curriculum design, pharmacy graduates will be well equipped to lead clinical pharmacogenomics in practice.
Topics: United States; Humans; Pharmacogenetics; Education, Pharmacy; Schools, Pharmacy; Curriculum; Pharmacists
PubMed: 38281827
DOI: 10.1016/j.cptl.2023.12.029 -
Journal of Chemotherapy (Florence,... May 2024Irinotecan is a critical anticancer drug used to treat metastatic colorectal cancer and advanced pancreatic ductal adenocarcinoma by obstructing topoisomerase 1;... (Review)
Review
Irinotecan is a critical anticancer drug used to treat metastatic colorectal cancer and advanced pancreatic ductal adenocarcinoma by obstructing topoisomerase 1; however, it can cause minor-to-severe and life-threatening adverse effects. UDP glucuronosyltransferase family 1 member A1 () polymorphisms increase the risk of irinotecan-induced neutropenia and diarrhea. Hence, screening for polymorphisms before irinotecan-based chemotherapy is recommended to minimize toxicity, whereas liposomes offer the potential to deliver irinotecan with fewer side effects in patients with pancreatic ductal adenocarcinoma. This review presents a comprehensive overview of the effects of genotype-guided dosing of irinotecan on and variants, incorporating pharmacogenomic research, optimal regimens for metastatic colorectal and pancreatic cancer treatment using irinotecan, guidelines for toxicity reduction, and an evaluation of the cost-effectiveness of genotype testing.
PubMed: 38706404
DOI: 10.1080/1120009X.2024.2349444 -
EBioMedicine Mar 2024Pharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology,...
BACKGROUND
Pharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology, demonstrating a beneficial effect of PGx-guided treatment in reducing adverse drug reactions, there are very few such studies in psychiatry, none of which spans across all main psychiatric indications, namely schizophrenia, major depressive disorder and bipolar disorder. In this study we aim to investigate the clinical effectiveness of PGx-guided treatment (occurrence of adverse drug reactions, hospitalisations and re-admissions, polypharmacy) and perform a cost analysis of the intervention.
METHODS
We report our findings from a multicenter, large-scale, prospective study of pre-emptive genome-guided treatment named as PREemptive Pharmacogenomic testing for preventing Adverse drug REactions (PREPARE) in a large cohort of psychiatric patients (n = 1076) suffering from schizophrenia, major depressive disorder and bipolar disorder.
FINDINGS
We show that patients with an actionable phenotype belonging to the PGx-guided arm (n = 25) present with 34.1% less adverse drug reactions compared to patients belonging to the control arm (n = 36), 41.2% less hospitalisations (n = 110 in the PGx-guided arm versus n = 187 in the control arm) and 40.5% less re-admissions (n = 19 in the PGx-guided arm versus n = 32 in the control arm), less duration of initial hospitalisations (n = 3305 total days of hospitalisation in the PGx-guided arm from 110 patients, versus n = 6517 in the control arm from 187 patients) and duration of hospitalisation upon readmission (n = 579 total days of hospitalisation upon readmission in the PGx-guided arm, derived from 19 patients, versus n = 928 in the control arm, from 32 patients respectively). It was also shown that in the vast majority of the cases, there was less drug dose administrated per drug in the PGx-guided arm compared to the control arm and less polypharmacy (n = 124 patients prescribed with at least 4 psychiatric drugs in the PGx-guided arm versus n = 143 in the control arm) and smaller average number of co-administered psychiatric drugs (2.19 in the PGx-guided arm versus 2.48 in the control arm. Furthermore, less deaths were reported in the PGx-guided arm (n = 1) compared with the control arm (n = 9). Most importantly, we observed a 48.5% reduction of treatment costs in the PGx-guided arm with a reciprocal slight increase of the quality of life of patients suffering from major depressive disorder (0.935 versus 0.925 QALYs in the PGx-guided and control arm, respectively).
INTERPRETATION
While only a small proportion (∼25%) of the entire study sample had an actionable genotype, PGx-guided treatment can have a beneficial effect in psychiatric patients with a reciprocal reduction of treatment costs. Although some of these findings did not remain significant when all patients were considered, our data indicate that genome-guided psychiatric treatment may be successfully integrated in mainstream healthcare.
FUNDING
European Union Horizon 2020.
Topics: Humans; Pharmacogenetics; Prospective Studies; Depressive Disorder, Major; Quality of Life; Psychiatry; Drug-Related Side Effects and Adverse Reactions
PubMed: 38364700
DOI: 10.1016/j.ebiom.2024.105009 -
Neurochemistry International Feb 2024Neuropsychiatric disorders are considered to be the most common cause of disability worldwide. Serotonin and its transporter is a prominent paradigm in mood disorders.... (Review)
Review
Neuropsychiatric disorders are considered to be the most common cause of disability worldwide. Serotonin and its transporter is a prominent paradigm in mood disorders. Response to selective serotonin reuptake inhibitors (SSRI) is altered due to heterogeneity in the serotonin transporter gene, SLC6A4 (solute carrier family 6 member 4). The reported polymorphisms are found to be in different regions of the transporter gene: promoter region (5-HTTLPR and various single nucleotide polymorphisms within it), intron (STin2), and exon 9 (I425V). The long and short alleles of the 5-HTTLPR gene, which are prevalent among variations, may mediate differential effects. In long allelic variant carriers, an increased response to SSRI and timely recovery is due to increased availability of SERT. Whereas, SERT availability is significantly decreased in short allelic carriers, necessitating a reduction in SSRI dosage due to the increased risk of adverse drug reactions. Thus, pharmacogenetic investigations are required to understand the impact of functional variations on the efficacy and tolerability of SSRI. Identifying the carrier variants may aid in clear-decision making of the treatment regimen, aiding the approach of personalized medication.
Topics: Selective Serotonin Reuptake Inhibitors; Serotonin; Pharmacogenetics; Serotonin Plasma Membrane Transport Proteins; Polymorphism, Single Nucleotide
PubMed: 38157886
DOI: 10.1016/j.neuint.2023.105672 -
Cancer Research Nov 2023Proteomics is a powerful approach that can rapidly enhance our understanding of cancer development. Detailed characterization of the genetic, pharmacogenomic, and immune...
UNLABELLED
Proteomics is a powerful approach that can rapidly enhance our understanding of cancer development. Detailed characterization of the genetic, pharmacogenomic, and immune landscape in relation to protein expression in patients with cancer could provide new insights into the functional roles of proteins in cancer. By taking advantage of the genotype data from The Cancer Genome Atlas and protein expression data from The Cancer Proteome Atlas, we characterized the effects of genetic variants on protein expression across 31 cancer types and identified approximately 100,000 protein quantitative trait loci (pQTL). Among these, over 8000 pQTLs were associated with patient overall survival. Furthermore, characterization of the impact of protein expression on more than 350 imputed anticancer drug responses in patients revealed nearly 230,000 significant associations. In addition, approximately 21,000 significant associations were identified between protein expression and immune cell abundance. Finally, a user-friendly data portal, GPIP (https://hanlaboratory.com/GPIP), was developed featuring multiple modules that enable researchers to explore, visualize, and browse multidimensional data. This detailed analysis reveals the associations between the proteomic landscape and genetic variation, patient outcome, the immune microenvironment, and drug response across cancer types, providing a resource that may offer valuable clinical insights and encourage further functional investigations of proteins in cancer.
SIGNIFICANCE
Comprehensive characterization of the relationship between protein expression and the genetic, pharmacogenomic, and immune landscape of tumors across cancer types provides a foundation for investigating the role of protein expression in cancer development and treatment.
Topics: Humans; Proteomics; Pharmacogenetics; Proteome; Genotype; Neoplasms; Tumor Microenvironment
PubMed: 37548539
DOI: 10.1158/0008-5472.CAN-23-0758 -
European Journal of Human Genetics :... Sep 2023
Topics: Humans; Irinotecan; Pharmacogenetics; Fluorouracil; Genotype; Drug Interactions
PubMed: 36750665
DOI: 10.1038/s41431-023-01306-y -
Pharmacology Research & Perspectives Dec 2023
Topics: Precision Medicine; Pharmacogenetics; Drug Discovery
PubMed: 37885364
DOI: 10.1002/prp2.1147 -
Journal of Cardiovascular Development... Dec 2023Ischemic stroke is a heterogeneous condition influenced by a combination of genetic and environmental factors. Recent advancements have explored genetics in relation to... (Review)
Review
Ischemic stroke is a heterogeneous condition influenced by a combination of genetic and environmental factors. Recent advancements have explored genetics in relation to various aspects of ischemic stroke, including the alteration of individual stroke occurrence risk, modulation of treatment response, and effectiveness of post-stroke functional recovery. This article aims to review the recent findings from genetic studies related to various clinical and molecular aspects of ischemic stroke. The potential clinical applications of these genetic insights in stratifying stroke risk, guiding personalized therapy, and identifying new therapeutic targets are discussed herein.
PubMed: 38132662
DOI: 10.3390/jcdd10120495 -
Clinical Pharmacology and Therapeutics Aug 2023Pharmacogenetics can improve clinical outcomes by reducing adverse drug effects and enhancing therapeutic efficacy for commonly used drugs that treat a wide range of...
Pharmacogenetics can improve clinical outcomes by reducing adverse drug effects and enhancing therapeutic efficacy for commonly used drugs that treat a wide range of cardiovascular diseases. One of the major barriers to the clinical implementation of cardiovascular pharmacogenetics is limited education on this field for current healthcare providers and students. The abundance of pharmacogenetic literature underscores its promise, but it can also be challenging to learn such a wealth of information. Moreover, current clinical recommendations for cardiovascular pharmacogenetics can be confusing because they are outdated, incomplete, or inconsistent. A myriad of misconceptions about the promise and feasibility of cardiovascular pharmacogenetics among healthcare providers also has halted clinical implementation. Therefore, the main goal of this tutorial is to provide introductory education on the use of cardiovascular pharmacogenetics in clinical practice. The target audience is any healthcare provider (or student) with patients that use or have indications for cardiovascular drugs. This tutorial is organized into the following 6 steps: (1) understand basic concepts in pharmacogenetics; (2) gain foundational knowledge of cardiovascular pharmacogenetics; (3) learn the different organizations that release cardiovascular pharmacogenetic guidelines and recommendations; (4) know the current cardiovascular drugs/drug classes to focus on clinically and the supporting evidence; (5) discuss an example patient case of cardiovascular pharmacogenetics; and (6) develop an appreciation for emerging areas in cardiovascular pharmacogenetics. Ultimately, improved education among healthcare providers on cardiovascular pharmacogenetics will lead to a greater understanding for its potential in improving outcomes for a leading cause of morbidity and mortality.
Topics: Humans; Pharmacogenetics; Cardiovascular Agents; Cardiovascular Diseases; Drug-Related Side Effects and Adverse Reactions; Health Personnel
PubMed: 37303270
DOI: 10.1002/cpt.2957