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Annual Review of Pharmacology and... Jan 2020Pharmacogenetics is a key component of precision medicine. Genetic variation in drug metabolism enzymes can lead to variable exposure to drugs and metabolites,... (Review)
Review
Pharmacogenetics is a key component of precision medicine. Genetic variation in drug metabolism enzymes can lead to variable exposure to drugs and metabolites, potentially leading to inefficacy and drug toxicity. Although the evidence for pharmacogenetic associations in children is not as extensive as for adults, there are several drugs across diverse therapeutic areas with robust pediatric data indicating important, and relatively common, drug-gene interactions. Guidelines to assist gene-based dose optimization are available for codeine, thiopurine drugs, selective serotonin reuptake inhibitors, atomoxetine, tacrolimus, and voriconazole. For each of these drugs, there is an opportunity to clinically implement precision medicine approaches with children for whom genetic test results are known or are obtained at the time of prescribing. For many more drugs that are commonly used in pediatric patients, additional investigation is needed to determine the genetic factors influencing appropriate dose.
Topics: Child; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmaceutical Preparations; Pharmacogenetics; Precision Medicine
PubMed: 31283429
DOI: 10.1146/annurev-pharmtox-010919-023459 -
Annales de Biologie Clinique Dec 2017The aim of this review is to provide a brief overview of personalized medicine, pharmacogenetics and companion tests. Personalized or stratified medicine is a new... (Review)
Review
The aim of this review is to provide a brief overview of personalized medicine, pharmacogenetics and companion tests. Personalized or stratified medicine is a new paradigm in the management of patients, aimed at better taking into account inter-individual variability. The response to drugs' intake varies considerably, depending on the transport and metabolism of the drugs, the target and the pathophysiological characteristics of the organism. Each stage is very variable and can be modified by endogenous factors (pathophysiology, age, sex, genetics…) or exogenous (environmental: taking other medicines, food, tobacco, alcohol…). Pharmacogenetics studies the genetic factors involved in the pharmacological or toxicological response to drugs. Companion tests that are often based on a pharmacogenetic principle aim to identify in a patient's population those who will respond to a given treatment.
Topics: Biological Variation, Population; Biomarkers, Pharmacological; Drug Resistance; Humans; Inactivation, Metabolic; Pharmacogenetics; Precision Medicine; Treatment Outcome
PubMed: 29192598
DOI: 10.1684/abc.2017.1306 -
Current Opinion in Anaesthesiology Dec 2018The current review will discuss the current literature on genetics of pain and analgesia, with special emphasis on perioperative setting. We will also discuss... (Review)
Review
PURPOSE OF REVIEW
The current review will discuss the current literature on genetics of pain and analgesia, with special emphasis on perioperative setting. We will also discuss pharmacogenetics-based management guidelines, current clinical status and future perspectives.
RECENT FINDINGS
Recent literature suggests that the interindividual variability in pain and postoperative analgesic response is at least in part because of one's genetic make-up. Some of the well characterized polymorphisms that are associated with surgical pain and opioid-related postoperative adverse outcomes are described in catechol-O-methyl transferase, CYP2D6 and μ-opioid receptor (OPRM1), ATP-binding cassette subfamily B member 1, ABCC3, organic cation transporter 1 genes. Clinical Pharmacogenetics Implementation Consortium has put forth recommendations on CYP2D6 genotype-based opioid selection and dosing. The list of drug-gene pairs studied continue to expand.
SUMMARY
Pharmacogenetic approach marks the dawn of personalized pain medicine both in perioperative and chronic pain settings.
Topics: Analgesia; Humans; Pain Management; Pain, Postoperative; Pharmacogenetics; Precision Medicine
PubMed: 30239351
DOI: 10.1097/ACO.0000000000000660 -
Mayo Clinic Proceedings Jan 2021Many practitioners who have not had pharmacogenomic education are required to apply pharmacogenomics to their practices. Although many aspects of pharmacogenomics are... (Review)
Review
Many practitioners who have not had pharmacogenomic education are required to apply pharmacogenomics to their practices. Although many aspects of pharmacogenomics are similar to traditional concepts of drug-drug interactions, there are some differences. We searched PubMed with the search terms pharmacogenomics and pharmacogenetics (January 1, 2005, through December 31, 2019) and selected articles that supported the application of pharmacogenomics to practice. For inclusion, we gave preference to national and international consortium guidelines for implementation of pharmacogenomics. We discuss special considerations important in the application of pharmacogenomics to assist clinicians with ordering, interpreting, and applying pharmacogenomics in their practices.
Topics: General Practitioners; Genetic Testing; Humans; Pharmacogenetics
PubMed: 33308868
DOI: 10.1016/j.mayocp.2020.03.011 -
Pharmacogenomics Feb 2021Pharmacogenetics represents a major driver of precision medicine, promising individualized drug selection and dosing. Traditionally, pharmacogenetic profiling has been... (Review)
Review
Pharmacogenetics represents a major driver of precision medicine, promising individualized drug selection and dosing. Traditionally, pharmacogenetic profiling has been performed using targeted genotyping that focuses on common/known variants. Recently, whole-genome sequencing (WGS) is emerging as a more comprehensive short-read next-generation sequencing approach, enabling both gene diagnostics and pharmacogenetic profiling, including rare/novel variants, in a single assay. Using the example of the pharmacogene , we demonstrate the potential of WGS-based pharmacogenetic profiling as well as emphasize the limitations of short-read next-generation sequencing. In the near future, we envision a shift toward long-read sequencing as the predominant method for gene diagnostics and pharmacogenetic profiling, providing unprecedented data quality and improving patient care.
Topics: Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Humans; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; Whole Genome Sequencing
PubMed: 33517770
DOI: 10.2217/pgs-2020-0155 -
Advances in Pharmacology (San Diego,... 2018Immunosuppressive drugs are a prerequisite in organ transplantation to prevent rejection and are also widely used in inflammatory diseases such as inflammatory bowel... (Review)
Review
Immunosuppressive drugs are a prerequisite in organ transplantation to prevent rejection and are also widely used in inflammatory diseases such as inflammatory bowel disease (IBD) or also in some hematologic malignancies-depending on the mode of action. For thiopurine analogs the polymorphic thiopurine S-methyltransferase (TPMT) was early detected to be associated with thiopurine-induced leukopenia; recent studies identified also NUDT15 to be related to this severe side effect. For drugs like methotrexate and mycophenolate mofetil a number of ADME genes like UDP-glucuronosyltransferases (UGTs) and ABC efflux transporters were investigated, however, with partly contradicting results. For calcineurin inhibitors like cyclosporine and in particular tacrolimus however, cytochrome P450 3A4 and 3A5 variants were found to significantly affect the pharmacokinetics. Genetic variants in genes encoding relevant pharmacodynamic proteins, however, lacked compelling evidence to affect the clinical outcome. This chapter reviews the current evidence on the association of pharmacogenetic traits to dose finding and clinical outcome of small-molecule immunosuppressants. Moreover this chapter critically summarizes suitability to apply pharmacogenetics in clinical practice in order to optimize immunosuppressant therapy.
Topics: Calcineurin Inhibitors; Humans; Immunosuppressive Agents; Immunotherapy; Models, Biological; Pharmacogenetics
PubMed: 29801578
DOI: 10.1016/bs.apha.2018.02.004 -
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 -
International Journal of Psychiatry in... Mar 2021The treatment of depression represents a major challenge for healthcare systems and choosing among the many available drugs without objective guidance criteria is an... (Review)
Review
The treatment of depression represents a major challenge for healthcare systems and choosing among the many available drugs without objective guidance criteria is an error-prone process. Recently, pharmacogenetic biomarkers entered in prescribing guidelines, giving clinicians the possibility to use this additional tool to guide prescription and improve therapeutic outcomes. This marked an important step towards precision psychiatry, which aim is to integrate biological and environmental information to personalise treatments. Only genetic variants in cytochrome enzymes are endorsed by prescribing guidelines, but in the future polygenic predictors of treatment outcomes may be translated into the clinic. The integration of genetics with other relevant information (e.g., concomitant diseases and treatments, drug plasma levels) could be managed in a standardised way through ad hoc software. The overcoming of the current obstacles (e.g., staff training, genotyping and informatics facilities) can lead to a broad implementation of precision psychiatry and represent a revolution for psychiatric care.Key pointsPrecision psychiatry aims to integrate biological and environmental information to personalise treatments and complement clinical judgementPharmacogenetic biomarkers in cytochrome genes were included in prescribing guidelines and represented an important step towards precision psychiatryTherapeutic drug monitoring is an important and cost-effective tool which should be integrated with genetic testing and clinical evaluation in order to optimise pharmacotherapyOther individual factors relevant to pharmacotherapy response (e.g., individual's symptom profile, concomitant diseases) can be integrated with genetic information through artificial intelligence to provide treatment recommendationsThe creation of pharmacogenetic services within healthcare systems is a challenging and multi-step process, education of health professionals, promotion by institutions and regulatory bodies, economic and ethical barriers are the main issues.
Topics: Antidepressive Agents; Artificial Intelligence; Depressive Disorder; Drug Monitoring; Humans; Pharmacogenetics; Precision Medicine; Psychiatry
PubMed: 32852246
DOI: 10.1080/13651501.2020.1809680 -
The Journal of Pharmacology and... Aug 2023The use of pharmacogenetic guidelines in personalizing treatments has shown the potential to reduce interindividual variability in drug response by enabling... (Review)
Review
The use of pharmacogenetic guidelines in personalizing treatments has shown the potential to reduce interindividual variability in drug response by enabling genotype-matched dosing and drug selection. However, other important factors, such as patient gender, may interact strongly with pharmacogenetics in determining the individual profile of toxicity and efficacy but are still rarely considered when planning pharmacological treatment. The literature indicates that males and females respond differently to drugs, with women being at higher risk for toxicity and having different plasma exposure to drugs at standard doses. Recent studies have shown that pharmacogenetic variants may have different predictive value in different sexes, as in the case of treatment with opioids, angiotensin-converting enzyme inhibitors, or proton pump inhibitors. Of particular interest is the case of treatment with fluoropyrimidines for cancer. A significant increase in toxicity has been described in female patients, with a more pronounced effect of specific and polymorphisms also noted. This manuscript reviews the major findings in the field of sex-specific pharmacogenomics. SIGNIFICANCE STATEMENT: Interindividual variability in drug response is an emerging issue in pharmacology. The genetic profile of patients, as well as their gender, may play a role in the identification of patients more exposed to the risk of adverse drug reactions or poor efficacy. This article reviews the current state of research on the interaction between gender and pharmacogenetics in addressing interindividual variability.
Topics: Female; Humans; Pharmacogenetics; Polymorphism, Genetic; Genotype; Neoplasms
PubMed: 37001987
DOI: 10.1124/jpet.122.001416 -
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