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Pharmacogenomics Jan 2024
Topics: Humans; Pharmacogenetics
PubMed: 38112072
DOI: 10.2217/pgs-2023-0228 -
Current Rheumatology Reports Oct 2023Axial spondyloarthritis (AxSpA) is among the rheumatology's most heritable complex diseases, yet precision medicine at clinics still needs to be explored. We reviewed... (Review)
Review
PURPOSE OF REVIEW
Axial spondyloarthritis (AxSpA) is among the rheumatology's most heritable complex diseases, yet precision medicine at clinics still needs to be explored. We reviewed the emerging concepts and recent developments in polygenic risk scores, Mendelian randomization, pharmacogenomics, single-cell sequencing, and spatial transcriptomics.
RECENT FINDINGS
Polygenic risk score has resulted in encouraging results with potential diagnostic utility as it appears to outperform current diagnostic tools. Its performance and generalizability vary with ethnicity. Mendelian randomization has elucidated multiple causal associations, particularly between inflammatory bowel disease and AxSpA. Single-cell transcriptomics (particularly scRNA-seq and scATAC-seq) has identified numerous cell types, including synovial and blood immunological cells, to understand the contribution of both innate and adaptative immunity in AxSpA. Current molecular tools provide an exciting opportunity to advance precision medicine for AxSpA patients. However, extensive research and implementation strategies are still required before they can have an impact in the clinic.
Topics: Humans; Spondylarthritis; Precision Medicine; Spondylitis, Ankylosing; Axial Spondyloarthritis; Risk Factors
PubMed: 37505349
DOI: 10.1007/s11926-023-01113-w -
Frontiers in Endocrinology 2023
Topics: Humans; Pharmacogenetics; Diabetes Mellitus, Type 2; Precision Medicine; Microbiota
PubMed: 37795358
DOI: 10.3389/fendo.2023.1287807 -
Frontiers in Pharmacology 2023With the trend towards promoting personalised medicine (PM), the application of pharmacogenetics and pharmacogenomics (PGx) is of growing importance. For the purposes of...
With the trend towards promoting personalised medicine (PM), the application of pharmacogenetics and pharmacogenomics (PGx) is of growing importance. For the purposes of clinical trials, the inclusion of PGx is an additional tool that should be considered for improving our knowledge about the effectiveness and safety of new drugs. A search of available clinical trials containing pharmacogenetic and PGx information was conducted on ClinicalTrials.gov. The results show there has been an increase in the number of trials containing PGx information since the 2000 s, with particular relevance in the areas of Oncology (28.43%) and Mental Health (10.66%). Most of the clinical trials focus on treatment as their primary purpose. In those clinical trials entries where the specific genes considered for study are detailed, the most frequently explored genes are (especially in Mental Health and Pain), (in Hematology), (in Cardiology and Mental Health) and and (particularly prominent in Transplantation and Cardiology), among others. Researchers and clinicans should be trained in pharmacogenetics and PGx in order to be able to make a proper interpretation of this data, contributing to better prescribing decisions and an improvement in patients' care, which would lead to the performance of PM.
PubMed: 37927590
DOI: 10.3389/fphar.2023.1247088 -
The Pharmacogenomics Journal May 2024Pharmacogenomics (PGx) research and applications are of utmost relevance in Lebanon considering its population genetic diversity. Moreover, as a country with regional... (Review)
Review
Pharmacogenomics (PGx) research and applications are of utmost relevance in Lebanon considering its population genetic diversity. Moreover, as a country with regional leadership in medicine and higher education, Lebanon holds a strong potential in contributing to PGx research and clinical implementation. In this manuscript, we first review and evaluate the available PGx research conducted in Lebanon, then describe the current status of PGx practice in Lebanon while reflecting on the local and regional challenges, and highlighting areas for action, and opportunities to move forward. We specifically expand on the status of PGx at the American University of Beirut Faculty of Medicine and Medical Center as a case study and guide for the further development of local and regional comprehensive PGx research, teaching, and clinical implementation programs. We also delve into the status of PGx knowledge and education, and prospects for further advancement such as with online courses and certificates.
Topics: Lebanon; Humans; Pharmacogenetics; Precision Medicine
PubMed: 38778046
DOI: 10.1038/s41397-024-00336-z -
Journal of Clinical Medicine Jul 2023Kidney transplantation is the preferred therapeutic option for end-stage kidney disease, but, despite major therapeutic advancements, allograft rejection continues to... (Review)
Review
Kidney transplantation is the preferred therapeutic option for end-stage kidney disease, but, despite major therapeutic advancements, allograft rejection continues to endanger graft survival. Every patient is unique due to his or her clinical history, drug metabolism, genetic background, and epigenetics. For this reason, examples of "personalized medicine" and "precision medicine" have steadily increased in recent decades. The final target of precision medicine is to maximize drug efficacy and minimize toxicity for each individual patient. Immunosuppressive drugs, in the setting of kidney transplantation, require a precise dosage to avoid either adverse events (overdosage) or a lack of efficacy (underdosage). In this review, we will explore the knowledge regarding the pharmacogenomics of the main immunosuppressive medications currently utilized in kidney transplantation. We will focus on clinically relevant pharmacogenomic data, that is, the polymorphisms of the genes that metabolize immunosuppressive drugs.
PubMed: 37445489
DOI: 10.3390/jcm12134454 -
Pharmacogenomics Oct 2023As substrates of CYP2C8, CYP3A4/5 and CYP2D6, chloroquine's (CQ) and hydroxychloroquine's (HCQ) efficacy and safety may be affected by variants in the genes encoding... (Review)
Review
As substrates of CYP2C8, CYP3A4/5 and CYP2D6, chloroquine's (CQ) and hydroxychloroquine's (HCQ) efficacy and safety may be affected by variants in the genes encoding these enzymes. This paper aims to assimilate the current evidence on the pharmacogenomics of CQ/HCQ and to identify risk phenotypes affecting the safety or efficacy of these drugs. It has been found that some , and genetic variants may affect the safety or effectiveness of CQ/HCQ. The phenotypes predictively representing ultra-rapid and poor metabolizers have been considered high-risk phenotypes. After considering these high-risk phenotypes in different ethnic groups, it is predicted that a considerable proportion of patients taking CQ/HCQ may be at risk of either therapeutic failure or severe toxicities.
Topics: Humans; Hydroxychloroquine; Chloroquine; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP2D6; Pharmacogenetics
PubMed: 37846548
DOI: 10.2217/pgs-2023-0124 -
Pharmacotherapy Jul 2023Solid organ transplant recipients are reliant on immunosuppressive drugs, which have a narrow therapeutic index, and are concurrently vulnerable to adverse drug events... (Review)
Review
Solid organ transplant recipients are reliant on immunosuppressive drugs, which have a narrow therapeutic index, and are concurrently vulnerable to adverse drug events due to comorbidity burden and the complexity of their medication regimens. Urgent management of post-transplant complications often falls to the generalist clinician or critical care specialist. The purpose of this narrative review is to discuss innovations and bedside applications of pharmacogenomics and therapeutic drug monitoring applied to immunosuppression and agents frequently encountered in transplant recipients. Medication formulations will be given specific attention, as interchange is frequently required in the acute care setting. Bioassays quantifying immune system activity will be described with practical applications. A structured approach to addressing drug-drug, drug-gene, and drug-drug-gene interactions will be modeled using a case-based approach synthesizing pharmacogenomics, therapeutic drug monitoring, pharmacokinetics, and pharmacodynamic principles.
Topics: Humans; Pharmacogenetics; Transplant Recipients; Immunosuppressive Agents; Immunosuppression Therapy; Organ Transplantation; Tacrolimus
PubMed: 36999337
DOI: 10.1002/phar.2798 -
Pharmaceuticals (Basel, Switzerland) Nov 2023Polymorphisms of genes encoding drug metabolizing enzymes and transporters can significantly modify pharmacokinetics, and this can be associated with significant... (Review)
Review
Polymorphisms of genes encoding drug metabolizing enzymes and transporters can significantly modify pharmacokinetics, and this can be associated with significant differences in drug efficacy, safety, and tolerability. Moreover, genetic variants of some components of the immune system can explain clinically relevant drug-related adverse events. However, the implementation of drug dose individualization based on pharmacogenomics remains scarce. In this narrative review, the impact of genetic variations on the disposition, safety, and tolerability of the most commonly prescribed drugs is reported. Moreover, reasons for poor implementation of pharmacogenomics in everyday clinical settings are discussed. The literature analysis showed that knowledge of how genetic variations can modify the effectiveness, safety, and tolerability of a drug can lead to the adjustment of usually recommended drug dosages, improve effectiveness, and reduce drug-related adverse events. Despite some efforts to introduce pharmacogenomics in clinical practice, presently very few centers routinely use genetic tests as a guide for drug prescription. The education of health care professionals seems critical to keep pace with the rapidly evolving field of pharmacogenomics. Moreover, multimodal algorithms that incorporate both clinical and genetic factors in drug prescribing could significantly help in this regard. Obviously, further studies which definitively establish which genetic variations play a role in conditioning drug effectiveness and safety are needed. Many problems must be solved, but the advantages for human health fully justify all the efforts.
PubMed: 38004461
DOI: 10.3390/ph16111596 -
Genes Nov 2023Dementia is a syndrome of global and progressive deterioration of cognitive skills, especially memory, learning, abstract thinking, and orientation, usually affecting... (Review)
Review
Dementia is a syndrome of global and progressive deterioration of cognitive skills, especially memory, learning, abstract thinking, and orientation, usually affecting the elderly. The most common forms are Alzheimer's disease, vascular dementia, and other (frontotemporal, Lewy body disease) dementias. The etiology of these multifactorial disorders involves complex interactions of various environmental and (epi)genetic factors and requires multiple forms of pharmacological intervention, including anti-dementia drugs for cognitive impairment, antidepressants, antipsychotics, anxiolytics and sedatives for behavioral and psychological symptoms of dementia, and other drugs for comorbid disorders. The pharmacotherapy of dementia patients has been characterized by a significant interindividual variability in drug response and the development of adverse drug effects. The therapeutic response to currently available drugs is partially effective in only some individuals, with side effects, drug interactions, intolerance, and non-compliance occurring in the majority of dementia patients. Therefore, understanding the genetic basis of a patient's response to pharmacotherapy might help clinicians select the most effective treatment for dementia while minimizing the likelihood of adverse reactions and drug interactions. Recent advances in pharmacogenomics may contribute to the individualization and optimization of dementia pharmacotherapy by increasing its efficacy and safety via a prediction of clinical outcomes. Thus, it can significantly improve the quality of life in dementia patients.
Topics: Humans; Aged; Pharmacogenetics; Quality of Life; Alzheimer Disease; Antidepressive Agents; Cognition
PubMed: 38002991
DOI: 10.3390/genes14112048