Pharmacogenomics: the genetics of variable drug responses.
Ontology highlight
ABSTRACT:
SUBMITTER: Roden DM
PROVIDER: S-EPMC3093198 | biostudies-literature | 2011 Apr
REPOSITORIES: biostudies-literature
Publications
Pharmacogenomics: the genetics of variable drug responses.
Roden Dan M DM Wilke Russell A RA Kroemer Heyo K HK Stein C Michael CM
Circulation 20110401 15
Similar Datasets
Project description: Not available
| S-EPMC4477265 | biostudies-literature
Project description:Vitamins are vital to sustain normal physiological function, metabolism, and growth for all living organisms. Being an integral component of coenzyme, vitamins can affect the catalytic activities of many enzymes and the expression of drug transporters. Genetic variations in metabolism and/or transporter genes of drugs can influence the exposure of the human body to drugs and/or their active metabolites, thus contributing to the variations in drug responses and toxicities. Nonetheless, pharmacogenomics studies on nutrients have been rarely summarized. In this article, we reviewed recent progress on vitamin pharmacogenomics, for a better understanding on the influence of vitamin-related gene polymorphisms on inter-individual differences in diseases and drug efficacy and safety.
| S-EPMC5414710 | biostudies-literature
Project description:Resistant hypertension (RHTN), defined as an uncontrolled blood pressure despite the use of multiple antihypertensive medications, is an increasing clinical problem associated with increased cardiovascular (CV) risk, including stroke and target organ damage. Genetic variability in blood pressure (BP)-regulating genes and pathways may, in part, account for the variability in BP response to antihypertensive agents, when taken alone or in combination, and may contribute to the RHTN phenotype. Pharmacogenomics focuses on the identification of genetic factors responsible for inter-individual variability in drug response. Expanding pharmacogenomics research to include patients with RHTN taking multiple BP-lowering medications may identify genetic markers associated with RHTN. To date, the available evidence surrounding pharmacogenomics in RHTN is limited and primarily focused on candidate genes. In this review, we summarize the most current data in RHTN pharmacogenomics and offer some recommendations on how to advance the field.
| S-EPMC4717470 | biostudies-literature
Project description:This basic review of genetic principles will aid pharmacists in preparing for their eventual role of translating gene-drug associations into clinical practice. Genes, which are stretches of deoxyribonucleic acid (DNA) contained on the 23 pairs of human chromosomes, determine the size and shape of every protein a living organism builds. Variation in pharmacogenes which encode for proteins central to drug action and toxicity serves as the basis of pharmacogenomics (PGx). Important online resources such as PharmGKB.org, cpicpgx.org, and PharmVar.org provide the clinician with curated and summarized PGx associations and clinical guidelines. As genetic testing becomes increasingly affordable and accessible, the time is now for pharmacists to embrace PGx-guided medication selection and dosing to personalize and improve the safety and efficacy of drug therapy.
| S-EPMC6891005 | biostudies-literature
Project description: Not available
| S-EPMC5828657 | biostudies-literature
Project description:Considerable progress has been made in identifying genetic risk factors for idiosyncratic adverse drug reactions in the past 30 years. These reactions can affect various tissues and organs, including liver, skin, muscle and heart, in a drug-dependent manner. Using both candidate gene and genome-wide association studies, various genes that make contributions of varying extents to each of these forms of reactions have been identified. Many of the associations identified for reactions affecting the liver and skin involve human leukocyte antigen (HLA) genes and for reactions relating to the drugs abacavir and carbamazepine, HLA genotyping is now in routine use prior to drug prescription. Other HLA associations are not sufficiently specific for translation but are still of interest in relation to underlying mechanisms for the reactions. Progress on non-HLA genes affecting adverse drug reactions has been less, but some important associations, such as those of SLCO1B1 and statin myopathy, KCNE1 and drug-induced QT prolongation and NAT2 and isoniazid-induced liver injury, are considered. Future prospects for identification of additional genetic risk factors for the various adverse drug reactions are discussed.
| S-EPMC3707028 | biostudies-literature
Project description:Natural genetic variation in the human genome is a cause of individual differences in responses to medications and is an underappreciated burden on public health. Although 108 G-protein-coupled receptors (GPCRs) are the targets of 475 (∼34%) Food and Drug Administration (FDA)-approved drugs and account for a global sales volume of over 180 billion US dollars annually, the prevalence of genetic variation among GPCRs targeted by drugs is unknown. By analyzing data from 68,496 individuals, we find that GPCRs targeted by drugs show genetic variation within functional regions such as drug- and effector-binding sites in the human population. We experimentally show that certain variants of μ-opioid and Cholecystokinin-A receptors could lead to altered or adverse drug response. By analyzing UK National Health Service drug prescription and sales data, we suggest that characterizing GPCR variants could increase prescription precision, improving patients' quality of life, and relieve the economic and societal burden due to variable drug responsiveness. VIDEO ABSTRACT.
| S-EPMC5766829 | biostudies-literature
Project description: Not available
| S-EPMC5828653 | biostudies-literature
Project description:The goal of individualized drug therapy requires physicians to be able to accurately predict an individual's response to a drug. Both genetic and environmental factors are known to influence drug response. 'Pharmacogenetics' is the study of the role of inheritance in variation in drug response phenotypes. Pharmacogenetics is now moving genome-wide to become 'pharmacogenomics', resulting in the recognition of novel biomarkers for individual variation in drug response. This article reviews the development, promise and challenges facing pharmacogenomics, using examples of drugs used to treat or prevent cardiovascular disease.
| S-EPMC3108370 | biostudies-literature
Project description:Precision medicine faces many challenges, including the gap of knowledge between disease genetics and pharmacogenomics (PGx). Disease genetics interprets the pathogenicity of genetic variants for diagnostic purposes, while PGx investigates the genetic influences on drug responses. Ideally, the quality of health care would be improved from the point of disease diagnosis to drug prescribing if PGx is integrated with disease genetics in clinical care. However, PGx genes or variants are usually not reported as a secondary finding even if they are included in a clinical genetic test for diagnostic purposes. This happens even though the detection of PGx variants can provide valuable drug prescribing recommendations. One underlying reason is the lack of systematic classification of the knowledge overlap between PGx and disease genetics. Here, we address this issue by analyzing gene and genetic variant annotations from multiple expert-curated knowledge databases, including PharmGKB, CPIC, ClinGen and ClinVar. We further classified genes based on the strength of evidence supporting a gene's pathogenic role or PGx effect as well as the level of clinical actionability of a gene. Twenty-six genes were found to have pathogenic variation associated with germline diseases as well as strong evidence for a PGx association. These genes were classified into four sub-categories based on the distinct connection between the gene's pathogenic role and PGx effect. Moreover, we have also found thirteen RYR1 genetic variants that were annotated as pathogenic and at the same time whose PGx effect was supported by a preponderance of evidence and given drug prescribing recommendations. Overall, we identified a nontrivial number of gene and genetic variant overlaps between disease genetics and PGx, which laid out a foundation for combining PGx and disease genetics to improve clinical care from disease diagnoses to drug prescribing and adherence.
| S-EPMC8772060 | biostudies-literature