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Neuroscience Letters May 2020Neurodegenerative disorders (NDDs)(Alzheimer's disease, Parkinson's disease) represent major problems of health in developed countries, with important psychosocial... (Review)
Review
Neurodegenerative disorders (NDDs)(Alzheimer's disease, Parkinson's disease) represent major problems of health in developed countries, with important psychosocial burden for families and high cost for the society. NDDs share some common pathogenic mechanisms such as age-related decline, multiple genetic defects distributed across the genome, deposits of abnormal proteins in the brain, and diverse environmental risk factors. Patients with NDDs currently receive polypharmacy with a high risk for drug-drug interactions and severe adverse drug events. Pharmacogenomics accounts for 60-90% variability in drug pharmacokinetics and pharmacodynamics. Major determinants of the pharmacogenomic outcome include pathogenic, mechanistic, metabolic, transporter and pleiotropic genes. The expression of these genes is under regulatory control of the epigenetic machinery. Approximately, 80% of the Caucasian population is deficient in the metabolization of drugs due to polymorphisms in metabolic genes; consequently, less than 40% of patients respond appropriately to conventional drugs. The implementation of pharmacogenomic procedures in the clinical practice may help to optimize therapeutics in NDDs.
Topics: Alzheimer Disease; Animals; Antiparkinson Agents; Dopamine Agents; Humans; Parkinson Disease; Pharmacogenetics; Polymorphism, Genetic
PubMed: 30236877
DOI: 10.1016/j.neulet.2018.09.018 -
Methods in Molecular Biology (Clifton,... 2022Pharmacogenetic testing in patients with cancer requiring cytotoxic chemotherapy offers the potential to predict, prevent, and mitigate chemotherapy-related toxicities.... (Review)
Review
Pharmacogenetic testing in patients with cancer requiring cytotoxic chemotherapy offers the potential to predict, prevent, and mitigate chemotherapy-related toxicities. While multiple drug-gene pairs have been identified and studied, few drug-gene pairs are currently used routinely in the clinical status. Here we review what is known, theorized, and unknown regarding the use of pharmacogenetic testing in cancer.
Topics: Humans; Neoplasms; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 36068461
DOI: 10.1007/978-1-0716-2573-6_4 -
Clinical Pharmacology and Therapeutics Nov 2019Precision medicine is an emerging framework to maximize therapeutic benefit by modifying the treatment for individual patients based on their variations in demographic,...
Precision medicine is an emerging framework to maximize therapeutic benefit by modifying the treatment for individual patients based on their variations in demographic, genomic, and environmental factors. In particular, "Pharmacogenomics" and "Therapeutic Drug Monitoring" are key elements of individualized drug treatment, staging Clinical Pharmacology at the forefront of precision medicine.
Topics: Drug Monitoring; Environment; Humans; Pharmacogenetics; Pharmacology, Clinical; Precision Medicine; Socioeconomic Factors
PubMed: 31584718
DOI: 10.1002/cpt.1622 -
Pharmacogenomics Apr 2020Tacrolimus is the gold standard immunosuppressant administered in solid organ and stem cell transplantation to avoid graft rejection post-transplant. Despite its... (Review)
Review
Tacrolimus is the gold standard immunosuppressant administered in solid organ and stem cell transplantation to avoid graft rejection post-transplant. Despite its widespread use, there is a large variation in response to therapy, likely due to high inter-individual pharmacokinetic variability. Therapeutic drug monitoring is employed to improve clinical response and reduce toxicity. There is substantial evidence that pharmacogenetics influences drug exposure and response. genotype significantly impacts oral tacrolimus concentrations and response after solid organ transplantation. There are fewer studies in stem cell transplantation and with intravenous tacrolimus dosing. This report highlights recent evidence suggesting genes such as and play a larger role after intravenous dosing compared with , and the role for novel genes on tacrolimus outcomes.
Topics: Drug Administration Routes; Humans; Immunosuppressive Agents; Pharmacogenetics; Stem Cell Transplantation; Tacrolimus
PubMed: 32308133
DOI: 10.2217/pgs-2019-0189 -
Genes Mar 2021Since the term "pharmacogenetics" was first published in the late 1950s by Friedrich Vogel, the field has evolved into genome-wide association studies identifying novel...
Since the term "pharmacogenetics" was first published in the late 1950s by Friedrich Vogel, the field has evolved into genome-wide association studies identifying novel variants associated with drug response phenotypes, international societies and consortia dedicated to pharmacogenomic research and clinical implementation, clinical practice guidelines, and the increasing availability of pharmacogenomic tests for healthcare providers in both hospital and primary care [...].
Topics: Genome-Wide Association Study; Humans; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 33801919
DOI: 10.3390/genes12030393 -
Animal Genetics Feb 2024The recent advances in high-throughput next-generation sequencing technologies have heralded the arrival of the Big Data era. As a result, the use of pharmacogenetics in... (Review)
Review
The recent advances in high-throughput next-generation sequencing technologies have heralded the arrival of the Big Data era. As a result, the use of pharmacogenetics in drug discovery and individualized drug therapy has transformed the field of precision medicine. This paradigm shift in drug development programs has effectively reshaped the old drug development practices, which were primarily concerned with the physiological status of patients for drug development. Pharmacogenomics bridges the gap between pharmacodynamics and pharmacokinetics, advancing current diagnostic and treatment strategies and enabling personalized and targeted drug therapy. The primary goals of pharmacogenetic studies are to improve drug efficacy and minimize toxicities, to identify novel drug targets, to estimate drug dosage for personalized medicine, and to incorporate it as a routine diagnostic for disease susceptibility. Although pharmacogenetics has numerous applications in individualized drug therapy and drug development, it is in its infancy in veterinary medicine. The objective of this review is to present an overview of historical landmarks, current developments in various animal species, challenges and future perspectives of genomics in drug development and dosage optimization for individualized medicine in veterinary subjects.
Topics: Animals; Pharmacogenetics; Precision Medicine; Genomics; High-Throughput Nucleotide Sequencing
PubMed: 37990577
DOI: 10.1111/age.13376 -
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 -
Methods in Molecular Biology (Clifton,... 2023Genetic variants can alter response to drugs and other therapeutic interventions. The study of this phenomenon, called pharmacogenomics, is similar in many ways to other...
Genetic variants can alter response to drugs and other therapeutic interventions. The study of this phenomenon, called pharmacogenomics, is similar in many ways to other types of genetic studies but has distinct methodological and statistical considerations. Genetic variants involved in the processing of exogenous compounds exhibit great diversity and complexity, and the phenotypes studied in pharmacogenomics are also more complex than typical genetic studies. In this chapter, we review basic concepts in pharmacogenomic study designs, data generation techniques, statistical analysis approaches, and commonly used methods and briefly discuss the ultimate translation of findings to clinical care.
Topics: Pharmacogenetics; Pharmacogenomic Testing; Phenotype; Research Design
PubMed: 36929083
DOI: 10.1007/978-1-0716-2986-4_14 -
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 -
Indian Journal of Pharmacology 2021Hypertension is a leading age-related disease in our society and if left untreated, leads to fatal cardiovascular complications. The prevalence of hypertension has... (Review)
Review
Hypertension is a leading age-related disease in our society and if left untreated, leads to fatal cardiovascular complications. The prevalence of hypertension has increased and becomes a significant global health economic burden, particularly in lower-income societies. Many loci associated with blood pressure and hypertension have been reported by genome-wide association studies that provided potential targets for pharmacotherapy. Pharmacogenetic research had shown interindividual variations in drug efficacy, safety, and tolerability. This could be due to genetic polymorphisms in the pharmacokinetics (genes involved in a transporter, plasma protein binding, and metabolism) or pharmacodynamic pathway (receptors, ion channels, enzymes). Pharmacogenetics promises great hope toward targeted therapy, but challenges remain in implementing pharmacogenetic aided antihypertensive therapy in clinical practice. Using various databases, we analyzed the underlying mechanisms between the candidate gene polymorphisms and antihypertensive drug interactions and the challenges of implementing precision medicine. We review the emergence of pharmacogenetics and its relevance to clinical pharmacological practice.
Topics: Antihypertensive Agents; Essential Hypertension; Genome-Wide Association Study; Humans; Pharmacogenetics; Polymorphism, Genetic
PubMed: 34414909
DOI: 10.4103/ijp.IJP_593_19