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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 -
Current Allergy and Asthma Reports Dec 2021Several genome-wide association studies (GWASs) of bronchodilator response (BDR) to albuterol have been published over the past decade. This review describes current... (Review)
Review
PURPOSE OF REVIEW
Several genome-wide association studies (GWASs) of bronchodilator response (BDR) to albuterol have been published over the past decade. This review describes current knowledge gaps, including pharmacogenetic studies of albuterol response in minority populations, effect modification of pharmacogenetic associations by age, and relevance of BDR phenotype characterization to pharmacogenetic findings. New approaches, such as leveraging additional "omics" data to focus pharmacogenetic interrogation, as well as developing polygenic risk scores in asthma treatment responses, are also discussed.
RECENT FINDINGS
Recent pharmacogenetic studies of albuterol response in minority populations have identified genetic polymorphisms in loci (DNAH5, NFKB1, PLCB1, ADAMTS3, COX18, and PRKG1), that are associated with BDR. Additional studies are needed to replicate these findings. Modification of the pharmacogenetic associations for SPATS2L and ASB3 polymorphisms by age has also been published. Evidence from metabolomic and epigenomic studies of BDR may point to new pharmacogenetic targets. Lastly, a polygenic risk score for response to albuterol has been developed but requires validation in additional cohorts. In order to expand our knowledge of pharmacogenetics of BDR, additional studies in minority populations are needed. Consideration of effect modification by age and leverage of other "omics" data beyond genomics may also help uncover novel pharmacogenetic loci for use in precision medicine for asthma treatment.
Topics: Albuterol; Bronchodilator Agents; Genome-Wide Association Study; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide
PubMed: 34958416
DOI: 10.1007/s11882-021-01023-w -
Clinical Pharmacology and Therapeutics Jan 2019Pharmacogenomics (PGx) can be seen as a model for biomedical studies: it includes all disease areas of interest and spans in vitro studies to clinical trials, while... (Review)
Review
Pharmacogenomics (PGx) can be seen as a model for biomedical studies: it includes all disease areas of interest and spans in vitro studies to clinical trials, while focusing on the relationships between genes and drugs and the resulting phenotypes. This review will examine different characteristics of PGx study publications and provide examples of excellence in framing PGx questions and reporting their resulting data in a way that maximizes the knowledge that can be built on them.
Topics: Humans; Periodicals as Topic; Pharmacogenetics; Terminology as Topic; Translational Research, Biomedical
PubMed: 30406943
DOI: 10.1002/cpt.1279 -
Clinical Biochemistry Sep 2014The experience of chronic pain is one of the commonest reasons individuals seek medical attention, making the management of chronic pain a major issue in clinical... (Review)
Review
OBJECTIVE
The experience of chronic pain is one of the commonest reasons individuals seek medical attention, making the management of chronic pain a major issue in clinical practice. Drug metabolism and responses are affected by many factors, with genetic variations offering only a partial explanation of an individual's response. There is a paucity of evidence for the benefits of pharmacogenetic testing in the context of pain management.
DESIGN AND METHODS
We reviewed the literature between 2000 and 2013, and references cited therein, using various keywords related to pain management, pharmacology and pharmacogenetics.
RESULTS
Opioids continue to be the mainstay of chronic pain management. Several non-opioid based therapies, such as treatment with cannabinoids, gene therapy and epigenetic-based approaches are now available for these patients. Adjuvant therapies with antidepressants, benzodiazepines or anticonvulsants can also be useful in managing pain. Currently, laboratory monitoring of pain management patients, if performed, is largely through urine drug measurements.
CONCLUSIONS
Drug half-life calculations can be used as functional markers of the cumulative effect of pharmacogenetics and drug-drug interactions. Assessment of half-life and therapeutic effects may be more useful than genetic testing in preventing adverse drug reactions to pain medications, while ensuring effective analgesia. Definitive, mass spectrometry-based methods, capable of measuring parent drug and metabolite levels, are the most useful assays for this purpose. Urine drug measurements do not necessarily correlate with serum drug concentrations or therapeutic effects. Therefore, they are limited in their use in monitoring efficacy and toxicity.
Topics: Adjuvants, Pharmaceutic; Analgesics, Opioid; Chronic Pain; Drug Interactions; Humans; Pain Management; Pharmacogenetics
PubMed: 24912048
DOI: 10.1016/j.clinbiochem.2014.05.065 -
Annual Review of Genomics and Human... Aug 2022Pharmacogenomic testing can be an effective tool to enhance medication safety and efficacy. Pharmacogenomically actionable medications are widely used, and approximately... (Review)
Review
Pharmacogenomic testing can be an effective tool to enhance medication safety and efficacy. Pharmacogenomically actionable medications are widely used, and approximately 90-95% of individuals have an actionable genotype for at least one pharmacogene. For pharmacogenomic testing to have the greatest impact on medication safety and clinical care, genetic information should be made available at the time of prescribing (preemptive testing). However, the use of preemptive pharmacogenomic testing is associated with some logistical concerns, such as consistent reimbursement, processes for reporting preemptive results over an individual's lifetime, and result portability. Lessons can be learned from institutions that have implemented preemptive pharmacogenomic testing. In this review, we discuss the rationale and best practices for implementing pharmacogenomics preemptively.
Topics: Genotype; Humans; Pharmacogenetics; Precision Medicine
PubMed: 35537468
DOI: 10.1146/annurev-genom-111621-102737 -
Drug Metabolism and Drug Interactions 2014Spanning over 2000 years, the Jewish population has a long history of migration, population bottlenecks, expansions, and geographical isolation, which has resulted in a... (Review)
Review
Spanning over 2000 years, the Jewish population has a long history of migration, population bottlenecks, expansions, and geographical isolation, which has resulted in a unique genetic architecture among the Jewish people. As such, many Mendelian disease genes and founder mutations for autosomal recessive diseases have been discovered in several Jewish groups, which have prompted recent genomic studies in the Jewish population on common disease susceptibility and other complex traits. Although few studies on the genetic determinants of drug response variability have been reported in the Jewish population, a number of unique pharmacogenetic variants have been discovered that are more common in Jewish populations than in other major racial groups. Notable examples identified in the Ashkenazi Jewish (AJ) population include the vitamin K epoxide reductase complex subunit 1 (VKORC1) c.106G>T (p.D36Y) variant associated with high warfarin dosing requirements and the recently reported cytochrome P450 2C19 (CYP2C19) allele, CYP2C19*4B, that harbors both loss-of-function [*4 (c.1A>G)] and increased-function [*17 (c.-806C>T)] variants on the same haplotype. These data are encouraging in that like other ethnicities and subpopulations, the Jewish population likely harbors numerous pharmacogenetic variants that are uncommon or absent in other larger racial groups and ethnicities. In addition to unique variants, common multi-ethnic variants in key drug metabolism genes (e.g., ABCB1, CYP2C8, CYP2C9, CYP2C19, CYP2D6, NAT2) have also been detected in the AJ and other Jewish groups. This review aims to summarize the currently available pharmacogenetics literature and discuss future directions for related research with this unique population.
Topics: Cytochrome P-450 Enzyme System; Humans; Jews; Pharmaceutical Preparations; Pharmacogenetics; Population Surveillance
PubMed: 24867283
DOI: 10.1515/dmdi-2013-0069 -
Trends in Pharmacological Sciences Oct 2022Recent advances in next-generation sequencing (NGS) have resulted in the identification of tens of thousands of rare pharmacogenetic variations with unknown functional... (Review)
Review
Recent advances in next-generation sequencing (NGS) have resulted in the identification of tens of thousands of rare pharmacogenetic variations with unknown functional effects. However, although such pharmacogenetic variations have been estimated to account for a considerable amount of the heritable variability in drug response and toxicity, accurate interpretation at the level of the individual patient remains challenging. We discuss emerging strategies and concepts to close this translational gap. We illustrate how massively parallel experimental assays, artificial intelligence (AI), and machine learning can synergize with population-scale biobank projects to facilitate the interpretation of NGS data to individualize clinical decision-making and personalized medicine.
Topics: Artificial Intelligence; High-Throughput Nucleotide Sequencing; Humans; Machine Learning; Pharmacogenetics; Precision Medicine
PubMed: 36008164
DOI: 10.1016/j.tips.2022.07.002 -
The Pharmacogenomics Journal Oct 2017Pharmacogenetics (PGx) has the potential to personalize pharmaceutical treatments. Many relevant gene-drug associations have been discovered, but PGx-guided treatment... (Review)
Review
Pharmacogenetics (PGx) has the potential to personalize pharmaceutical treatments. Many relevant gene-drug associations have been discovered, but PGx-guided treatment needs to be cost-effective as well as clinically beneficial to be incorporated into standard health-care. We reviewed economic evaluations for PGx associations listed in the US Food and Drug Administration (FDA) Table of Pharmacogenomic Biomarkers in Drug Labeling. We determined the proportion of evaluations that found PGx-guided treatment to be cost-effective or dominant over the alternative strategies, and estimated the impact on this proportion of removing the cost of genetic testing. Of the 137 PGx associations in the FDA table, 44 economic evaluations, relating to 10 drugs, were identified. Of these evaluations, 57% drew conclusions in favour of PGx testing, of which 30% were cost-effective and 27% were dominant (cost-saving). If genetic information was freely available, 75% of economic evaluations would support PGx-guided treatment, of which 25% would be cost-effective and 50% would be dominant. Thus, PGx-guided treatment can be a cost-effective and even a cost-saving strategy. Having genetic information readily available in the clinical health record is a realistic future prospect, and would make more genetic tests economically worthwhile.
Topics: Cost-Benefit Analysis; Economics, Pharmaceutical; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; United States; United States Food and Drug Administration
PubMed: 28607506
DOI: 10.1038/tpj.2017.21 -
Biomedicine & Pharmacotherapy =... Jun 2022Mendelian randomization (MR) is an epidemiological method that uses genetic variants to proxy an exposure predicting its causal association with an outcome. It occupies... (Review)
Review
Mendelian randomization (MR) is an epidemiological method that uses genetic variants to proxy an exposure predicting its causal association with an outcome. It occupies a valuable niche between observational studies and randomized trials. MR applications expanded lately, facilitated by the availability of big data, to include disease risk causation prediction, supporting evidence of prior observational data, identifying new drug targets, and drug repurposing. Concurrently, the last decade witnessed the growth of pharmacogenomics (PGx) research as a cornerstone in precision medicine. PGx research, conducted at discovery and implementation levels, resulted in validated PGx biomarkers and tests. Despite many clinically relevant PGx associations that could be translated into clinical applications, worldwide implementation is lagging far behind. The current review examines the intersection zones between MR and PGx research. MR can provide supporting evidence that allows generalizing PGx findings supporting its implementation. Interchangeability, PGx research can fuel MR studies with libraries of genetic variants of validated biological relevance. Furthermore, PGx and MR exhibit a synergistic relationship in drug discovery that can accelerate identifying new targets and repurposing old drugs. Interdisciplinary research applied by PGx researchers, epidemiologists with MR experience, and data scientists' collaborations can unlock unforeseen opportunities in accelerating precision medicine acquisition.
Topics: Drug Discovery; Mendelian Randomization Analysis; Pharmacogenetics; Precision Medicine
PubMed: 35429744
DOI: 10.1016/j.biopha.2022.112952 -
Clinical Pharmacology and Therapeutics Apr 2020Clinical translation of drug-drug interaction (DDI) studies is limited, and knowledge gaps across different types of DDI evidence make it difficult to consolidate and... (Review)
Review
Clinical translation of drug-drug interaction (DDI) studies is limited, and knowledge gaps across different types of DDI evidence make it difficult to consolidate and link them to clinical consequences. Consequently, we developed information retrieval (IR) models to retrieve DDI and drug-gene interaction (DGI) evidence from 25 million PubMed abstracts and distinguish DDI evidence into in vitro pharmacokinetic (PK), clinical PK, and clinical pharmacodynamic (PD) studies for US Food and Drug Administration (FDA) approved and withdrawn drugs. Additionally, information extraction models were developed to extract DDI-pairs and DGI-pairs from the IR-retrieved abstracts. An overlapping analysis identified 986 unique DDI-pairs between all 3 types of evidence. Another 2,157 and 13,012 DDI-pairs and 3,173 DGI-pairs were identified from known clinical PK/PD DDI, clinical PD DDI, and DGI evidence, respectively. By integrating DDI and DGI evidence, we discovered 119 and 18 new pharmacogenetic hypotheses associated with CYP3A and CYP2D6, respectively. Some of these DGI evidence can also aid us in understanding DDI mechanisms.
Topics: Data Mining; Drug Interactions; Humans; Knowledge Discovery; Pharmacogenetics; Translational Research, Biomedical; United States; United States Food and Drug Administration
PubMed: 31863452
DOI: 10.1002/cpt.1745