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Pharmacotherapy Sep 2017Interindividual variability in response to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, with regard to both efficacy and safety is an obvious... (Review)
Review
Interindividual variability in response to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, with regard to both efficacy and safety is an obvious target for pharmacogenetic research. Many genes have been identified as possible contributors to variability in statin response and safety. Genetic polymorphisms may alter the structure or expression of coded proteins, with potential impacts on lipid and statin absorption, distribution, metabolism, and elimination as well as response pathways related to the pharmacologic effect. Many studies have explored the variation in statins' pharmacokinetic and pharmacodynamic parameters; however, to our knowledge, few have established definitive relationships between the genetic polymorphisms and patient outcomes, such as cardiovascular events. In this review article, we provide a statin-based summary of available evidence describing pharmacogenetic associations that may be of clinical relevance in the future. Although currently available studies are often small or retrospective, and may have conflicting results, they may be useful in providing direction for future confirmatory studies and may point to associations that could be confirmed in the future when more patient outcomes-based studies are available. We also summarize the clinically relevant evidence currently available to assist clinicians with providing personalized pharmacotherapy for patients requiring statin therapy.
Topics: Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pharmacogenetics; Polymorphism, Genetic; Treatment Outcome
PubMed: 28672099
DOI: 10.1002/phar.1981 -
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 -
British Medical Bulletin Dec 2017Pharmacogenetics is not a new subject area but its relevance to drug prescribing has become clearer in recent years due to developments in gene cloning and DNA... (Review)
Review
BACKGROUND
Pharmacogenetics is not a new subject area but its relevance to drug prescribing has become clearer in recent years due to developments in gene cloning and DNA genotyping and sequencing.
SOURCES OF DATA
There is a very extensive published literature concerned with a variety of different genes and drugs.
AREAS OF AGREEMENT
There is general agreement that pharmacogenetic testing is essential for the safe use of drugs such as the thiopurines and abacavir.
AREAS OF CONTROVERSY
Whether pharmacogenetic testing should be applied more widely including to the prescription of certain drugs such as warfarin and clopidogrel where the overall benefit is less clear remains controversial.
GROWING POINTS
Personal genotype information is increasingly being made available directly to the consumer. This is likely to increase demand for personalized prescription and mean that prescribers need to take pharmacogenetic information into account. Projects such as 100 000 genomes are providing complete genome sequences that can form part of a patient medical record. This information will be of great value in personalized prescribing.
AREAS TIMELY FOR DEVELOPING RESEARCH
Development of new drugs targeting particular genetic risk factors for disease. These could be prescribed to those with an at risk genotype.
Topics: Evidence-Based Medicine; Humans; Molecular Targeted Therapy; Pharmacogenetics; Pharmacogenomic Testing; Practice Guidelines as Topic; Precision Medicine; Risk Assessment
PubMed: 29040422
DOI: 10.1093/bmb/ldx035 -
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 -
Pharmacogenomics May 2018This Perspective provides examples of current and future applications of deep learning in pharmacogenomics, including: identification of novel regulatory variants... (Review)
Review
This Perspective provides examples of current and future applications of deep learning in pharmacogenomics, including: identification of novel regulatory variants located in noncoding domains of the genome and their function as applied to pharmacoepigenomics; patient stratification from medical records; and the mechanistic prediction of drug response, targets and their interactions. Deep learning encapsulates a family of machine learning algorithms that has transformed many important subfields of artificial intelligence over the last decade, and has demonstrated breakthrough performance improvements on a wide range of tasks in biomedicine. We anticipate that in the future, deep learning will be widely used to predict personalized drug response and optimize medication selection and dosing, using knowledge extracted from large and complex molecular, epidemiological, clinical and demographic datasets.
Topics: Algorithms; Databases as Topic; Deep Learning; Humans; Models, Educational; Neural Networks, Computer; Pharmacogenetics
PubMed: 29697304
DOI: 10.2217/pgs-2018-0008 -
Pharmacogenomics Nov 2018Despite the introduction of direct acting oral anticoagulants, warfarin remains the most commonly prescribed oral anticoagulant. However, warfarin therapy is plagued by... (Review)
Review
Despite the introduction of direct acting oral anticoagulants, warfarin remains the most commonly prescribed oral anticoagulant. However, warfarin therapy is plagued by the large inter- and intrapatient variability. The variability in dosing fueled research to identify clinical and genetic predictors and develop more accurate dosing algorithms. Observational studies have demonstrated the significant impact of single nucleotide polymorphisms in CYP2C9 and VKORC1 on warfarin dose in patients of European ancestry and African-Americans. This evidence supported the design and conduct of clinical trials to assess whether genotype-guided dosing results in improved anticoagulation control and outcomes. The trial results have shown discordance by race, with pharmacogenetic algorithms improving dose and anticoagulation control among European ancestry patients compared with African-American patients. Herein, we review the evidence from observational and interventional studies, highlight the need for inclusion of minority race groups and propose the need to develop race specific dosing algorithms.
Topics: Anticoagulants; Black People; Dose-Response Relationship, Drug; Genotype; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Warfarin; White People
PubMed: 30345882
DOI: 10.2217/pgs-2018-0146 -
PloS One 2018Pharmacogenetics practice has been successfully implemented in many developed countries to enhance personalized medicine and improve clinical and economic outcomes. An...
BACKGROUND
Pharmacogenetics practice has been successfully implemented in many developed countries to enhance personalized medicine and improve clinical and economic outcomes. An understanding of healthcare providers' knowledge, perceptions, confidence towards pharmacogenetics, and their active enrollment with pharmacogenetic testing is essential for test acceptance and utilization. This study was designed to assess physicians' and pharmacists' knowledge, perceptions, and confidence towards pharmacogenetics, determine the preferred learning format for their future education in pharmacogenetics, and identify the barriers to its application in their practice settings.
METHODS
A cross-sectional survey was conducted using a pretested self-administered questionnaire on a sample of 629 randomly selected physicians and pharmacists. Descriptive and comparative analyses were used in data analysis.
RESULTS
The response rate was 98.1%. Less than one-tenth of respondents were exposed to pharmacogenetics education or training (8.9%), applied pharmacogenetics testing in their practice (9.4%), or provided patient counselling on the results of the pharmacogenetic testing (9.1%), and over 90% of them were physicians. The overall respondents' mean (SD) total knowledge score percentage was low [45.0% (24)] and there was no significant difference between the physicians and pharmacists scores (p>0.05). Only 16.0% of participants indicated that they felt confident in applying pharmacogenetics in their practice settings. Despite these low levels of knowledge and self-confidence, 70.2% of participants expressed overall positive perceptions towards pharmacogenetics and its clinical implications. These positive overall perceptions were found to be significantly more common among pharmacists compared to physicians (p<0.05). The top two perceived barriers facing the implementation of pharmacogenetics in Kuwait were lack of education or training and clinical guidelines.
CONCLUSIONS
These findings highlight important concerns and will aid in the assessment of current pharmacogenetics practice. Also, they will provide further insight in designing future targeted multifaceted interventions to promote the adoption and utilization of pharmacogenetics testing in Kuwait.
Topics: Adult; Attitude of Health Personnel; Cross-Sectional Studies; Female; Genetic Testing; Health Knowledge, Attitudes, Practice; Humans; Kuwait; Male; Pharmacists; Pharmacogenetics; Physicians; Precision Medicine
PubMed: 30183746
DOI: 10.1371/journal.pone.0203033 -
Journal of Clinical Oncology : Official... Aug 2023
Topics: Humans; Pharmacogenomic Testing; Informed Consent; Pharmacogenetics; Genetic Testing
PubMed: 37267582
DOI: 10.1200/JCO.23.00664 -
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 -
Pharmacotherapy Jul 2023Pharmacogenetic testing for psychiatry is growing at a rapid pace, with multiple sites utilizing results to help clinical decision-making. Genotype-guided dosing and... (Review)
Review
Pharmacogenetic testing for psychiatry is growing at a rapid pace, with multiple sites utilizing results to help clinical decision-making. Genotype-guided dosing and drug selection have been implemented at several sites, including Vanderbilt University Medical Center, where clinical decision support (CDS) based on pharmacogenetic results went live for selective serotonin reuptake inhibitors in 2020 for both adult and pediatric patients. Effective and appropriate implementation of CYP2D6- and CYP2C19-guided CDS for the pediatric population requires consideration of the evidence for the pharmacogenetic associations, medication indications, and appropriate alternative therapies to be used when a pharmacogenetic contraindication is identified. In this article, we review these pediatric pharmacogenetic considerations for selective serotonin reuptake inhibitor CDS. We include a case study, the current literature supporting clinical recommendations, considerations when designing pediatric CDS, future implications, and examples of sertraline, (es)citalopram, paroxetine, and fluvoxamine alerts.
Topics: Adult; Humans; Child; Selective Serotonin Reuptake Inhibitors; Pharmacogenetics; Decision Support Systems, Clinical; Fluvoxamine; Citalopram
PubMed: 36524442
DOI: 10.1002/phar.2751