Background: This study examined clinical, demographic, anthropometric, and inheritance factors that influence individual sensitivity to warfarin therapy after heart valve surgery. The clinical significance of the pharmacogenetic approach was assessed using the individual time frame and time spent in the INR therapeutic range.
Aims: We determined the clinical outcome of the pharmacogenetic approach at the start of warfarin therapy in patients with prosthetic heart valves.
Materials And Methods: The study included 915 patients, of which 512 women and 403 men (mean age 56±10 years), living in Western Siberia. Rheumatic heart disease was the main diagnosis that caused the acquired defect. Mechanical prostheses were used in 70% of cases of cardiac surgery. Real-time polymerase chain reaction used for molecular genetic testing.
Results: The frequencies of the alleles and genotypes of CYP2C9 and VKORC1 in the study population of patients with heart valves prosthetic correspond to the distribution in Caucasoid populations. The use of pharmacogenetic testing results at the beginning of warfarin therapy reduced the time required for selecting a therapeutic dose of anticoagulant by 2 times and increased the duration of stay in the INR therapeutic range by 20.2%.
Conclusion: The use of the pharmacogenetic approach at the begin‑ ning of warfarin therapy contributes to the effectiveness and safety of anticoagulant therapy in this category of patients.
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http://dx.doi.org/10.18087/cardio.n681 | DOI Listing |
Eur J Pharmacol
January 2025
Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia. Electronic address:
Background And Purpose: Psilocybin is a serotonergic psychedelic with therapeutic potential for several neuropsychiatric disorders, including depression and anxiety disorders. Serotonin-transporter (5-HTT) knockout mice (KO) are a well-validated mouse model of anxiety/depression and are relevant to both chronic treatment with serotonin transporter reuptake inhibitors (SSRIs) and polymorphisms in the serotonin transporter-linked polymorphic region (5-HTTLPR) associated with depression/anxiety and resistance to classic antidepressant treatments. However, there is yet to be a study assessing the effect of psilocybin in 5-HTT KO mice.
View Article and Find Full Text PDFCurr Issues Mol Biol
December 2024
Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USA.
Tacrolimus and mycophenolate are important immunosuppressive agents used to prevent organ rejection in post-transplant patients. While highly effective, their use is associated with significant toxicity, requiring careful management. Tacrolimus, a calcineurin inhibitor, is linked to nephrotoxicity, neurotoxicity, metabolic disturbances such as diabetes mellitus and dyslipidemia, and cardiovascular complications such as hypertension and arrhythmias.
View Article and Find Full Text PDFGenome Med
January 2025
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA.
Background: Large-scale pharmacogenomic resources, such as the Connectivity Map (CMap), have greatly assisted computational drug discovery. However, despite their widespread use, CMap-based methods have thus far been agnostic to the biological activity of drugs as well as to the genomic effects of drugs in multiple disease contexts. Here, we present a network-based statistical approach, Pathopticon, that uses CMap to build cell type-specific gene-drug perturbation networks and integrates these networks with cheminformatic data and diverse disease phenotypes to prioritize drugs in a cell type-dependent manner.
View Article and Find Full Text PDFPharmacogenet Genomics
January 2025
Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan.
Ibrutinib treatment is often complicated by cardiovascular side effects (CVSEs). The objective of this retrospective pharmacogenetic study is to replicate a previously reported association of 'high-risk' patients, who are homozygous carriers of at least two of GATA4 rs804280 AA, KCNQ1 rs163182 GG, and KCNQ1 rs2237895 AA, with increased risk of hypertension or atrial fibrillation, and explore associations for other pharmacogenes (e.g.
View Article and Find Full Text PDFBiometrics
January 2025
Department of Statistics and Data Science, National University of Singapore, Singapore 117546, Singapore.
Pharmacogenomics stands as a pivotal driver toward personalized medicine, aiming to optimize drug efficacy while minimizing adverse effects by uncovering the impact of genetic variations on inter-individual outcome variability. Despite its promise, the intricate landscape of drug metabolism introduces complexity, where the correlation between drug response and genes can be shaped by numerous nongenetic factors, often exhibiting heterogeneity across diverse subpopulations. This challenge is particularly pronounced in datasets such as the International Warfarin Pharmacogenetic Consortium (IWPC), which encompasses diverse patient information from multiple nations.
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