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Pharmacogenetic

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https://www.readbyqxmd.com/read/29777729/pharmacogenetic-tests-to-guide-drug-treatment-in-depression-comparison-of-the-available-testing-kits-and-clinical-trials
#1
REVIEW
Chiara Fabbri, Joseph Zohar, Alessandro Serretti
The empirical approach to drug choice and dosing in depression often results into inadequate response and side effects. Pharmacogenetic (PGx) testing appears a promising way to implement personalized treatments. A systematic review was performed to identify available PGx tests, compare the genes they include with clinical guidelines and drug labels, and assess the quality of published clinical studies. ~40 commercial PGx tests are available and potential benefits were estimated for nine of them by clinical studies...
May 16, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29777510/clopidogrel-pharmacogenetics-in-iranian-patients-undergoing-percutaneous-coronary-intervention
#2
Nejat Mahdieh, Ahmad Rabbani, Ata Firouzi, Ali Zahedmehr, Maryam Hoseinimoghaddam, Sedigheh Saeidi, Hamidreza Sanati, Hosseinali Basiri, Feridoun Noohi, Bahareh Rabbani, Majid Maleki
Clopidogrel is used in patients with coronary syndromes and at risk of thrombotic events or receiving percutaneous coronary intervention (PCI) for reducing heart attack and stroke. Here we present genotype and phenotype study of Iranian patients undergoing PCI treated with clopidogrel during a 6-month period of follow-up; common variants of CYP2C19, CYP3A5, CYP3A4, and ABCB1 genes were determined as well as the patients' cardiovascular outcomes to find out the effect of these variants individually and in combination...
May 18, 2018: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29775551/pharmacogenetic-associations-with-cytochrome-p450-in-antiretroviral-therapy-what-does-the-future-hold
#3
Gabriel Stillemans, Leila Belkhir, Dennis A Hesselink, Vincent Haufroid, Laure Elens
Several antiretroviral drugs used to treat infection with the Human Immunodeficiency Virus (HIV) are substrates of enzymes belonging to the cytochrome P450 (CYP) superfamily, which are polymorphically expressed. It may therefore be useful to take into account the genetic variation in these enzymes to predict the likelihood of anti-HIV treatment success, toxicity and the potential for drug-drug interactions. Areas covered: In this manuscript, the authors discuss the current state of knowledge regarding pharmacogenetic associations between CYP and all major antiretrovirals, as well as the importance of these associations...
May 18, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29771919/firing-rate-based-network-modeling-of-the-dlgn-circuit-effects-of-cortical-feedback-on-spatiotemporal-response-properties-of-relay-cells
#4
Milad Hobbi Mobarhan, Geir Halnes, Pablo Martínez-Cañada, Torkel Hafting, Marianne Fyhn, Gaute T Einevoll
Visually evoked signals in the retina pass through the dorsal geniculate nucleus (dLGN) on the way to the visual cortex. This is however not a simple feedforward flow of information: there is a significant feedback from cortical cells back to both relay cells and interneurons in the dLGN. Despite four decades of experimental and theoretical studies, the functional role of this feedback is still debated. Here we use a firing-rate model, the extended difference-of-Gaussians (eDOG) model, to explore cortical feedback effects on visual responses of dLGN relay cells...
May 17, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29768302/pharmacogenomics-in-papua-new-guineans-unique-profiles-and-implications-for-enhancing-drug-efficacy-while-improving-drug-safety
#5
Joseph D Tucci, Paul P Pumuye, Nuala A Helsby, Daniel T Barratt, Percy P Pokeya, Francis Hombhanje, Andrew A Somogyi
Papua New Guinea (PNG) can be roughly divided into highland, coastal and island peoples with significant mitochondrial DNA differentiation reflecting early and recent distinct migrations from Africa and East Asia, respectively. Infectious diseases such as tuberculosis, malaria and HIV severely impact on the health of its peoples for which drug therapy is the major treatment and pharmacogenetics has clinical relevance for many of these drugs. Although there is generally little information about known single nucleotide polymorphisms in the population, in some instances, their frequencies have been shown to be higher than anywhere worldwide...
June 2018: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/29767545/pharmacogenetics-of-novel-oral-anticoagulants-a-review-of-identified-gene-variants-future-perspectives
#6
Adna Ašić, Damir Marjanović, Jure Mirat, Dragan Primorac
Novel oral anticoagulants (NOACs) are becoming a therapy of choice in everyday clinical practice after almost 50 years during which warfarin and related coumarin derivatives were used as the main anticoagulants. Advantages of NOACs over standard anticoagulants include their predictable pharmacodynamics and pharmacokinetics, stable plasma concentrations and less drug-drug and food-drug interactions. However, pharmacogenetics has its place in administration of NOACs, as considerable interindividual variations have been detected...
May 16, 2018: Personalized Medicine
https://www.readbyqxmd.com/read/29767472/the-impact-of-real-world-cardiovascular-related-pharmacogenetic-testing-in-an-insured-population
#7
Jennifer Billings, Patrick N Racsa, Kristine Bordenave, Charron L Long, Jeffrey J Ellis
BACKGROUND: Pharmacogenomics is intended to help clinicians provide the right drug to the right patient at an appropriate dose. However, limited evidence of clinical utility has slowed uptake of pharmacogenomic testing (PGT). OBJECTIVE: To evaluate the impact of real-world cardiovascular (CV)-related PGT on clinical outcomes, healthcare resource utilisation (HCRU) and cost in a large, heterogeneous population. METHODS: Individuals with Medicare Advantage Prescription Drug, Medicaid, or commercial coverage between 1/1/2011 and 9/30/2015 and ≥1 atherosclerotic CV-related diagnosis were identified...
May 16, 2018: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/29764354/impact-of-ethnicity-on-the-natural-history-of-parkinson-disease
#8
Anna Sauerbier, Azman Aris, Ee Wei Lim, Kalyan Bhattacharya, K Ray Chaudhuri
Parkinson disease (PD) affects people of all races and ethnicity worldwide. PD is a multineurotransmitter and multisystem disorder and our current concept of the natural history of PD has changed considerably over the past decades. Many aspects of this heterogeneous condition still remain unexplained; one aspect that is poorly studied is the role of ethnicity and manifest motor and non-motor PD. Some preliminary data suggest that the prodromal risk of developing PD, clinical symptom expression and the experience of living with the condition may vary between different ethnic groups...
May 21, 2018: Medical Journal of Australia
https://www.readbyqxmd.com/read/29761486/treatment-of-atopic-eczema-treat-registry-taskforce-an-international-delphi-exercise-to-identify-a-core-set-of-domains-and-domain-items-for-national-atopic-eczema-photo-and-systemic-therapy-registries
#9
L A A Gerbens, C J Apfelbacher, A D Irvine, S Barbarot, R J de Booij, A E Boyce, M Deleuran, L F Eichenfield, M H Hof, M A Middelkamp-Hup, A Roberts, J Schmitt, C Vestergaard, D Wall, S Weidinger, P R Williamson, C Flohr, P I Spuls
BACKGROUND: Evidence of immunomodulatory therapies to guide clinical management for atopic eczema (AE) is scarce, despite frequent and often off-label use. Patient registries provide valuable evidence for the effects of treatments under real world conditions which can inform treatment guidelines, give the opportunity for health economic evaluation and the evaluation of quality of care, as well as pharmacogenetic and -dynamic research which cannot be adequately addressed in clinical trials...
May 15, 2018: British Journal of Dermatology
https://www.readbyqxmd.com/read/29754666/a-genotype-directed-comparative-effectiveness-trial-of-bucindolol-and-metoprolol-succinate-for-prevention-of-symptomatic-atrial-fibrillation-atrial-flutter-in-patients-with-heart-failure-rationale-and-design-of-the-genetic-af-trial
#10
Jonathan P Piccini, Stuart J Connolly, William T Abraham, Jeff S Healey, Benjamin A Steinberg, Hussein R Al-Khalidi, Patricia Dignacco, Dirk J van Veldhuisen, William H Sauer, Michel White, Stephen B Wilton, Inder S Anand, Christopher Dufton, Debra A Marshall, Ryan G Aleong, Gordon W Davis, Richard L Clark, Laura L Emery, Michael R Bristow
BACKGROUND: Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials...
May 2018: American Heart Journal
https://www.readbyqxmd.com/read/29745250/genetic-differentiation-in-a-sample-from-northern-mexico-city-detected-by-hla-system-analysis-impact-in-the-study-of-population-immunogenetics
#11
Eva D Juárez Cortés, Miguel A Contreras Sieck, Agustín J Arriaga Perea, Rosa M Macías Medrano, Anaí Balbuena Jaime, Paola Everardo Martínez, Joaquín Zúñiga, Víctor Acuña Alonzo, Julio Granados, Rodrigo Barquera
The major histocompatibility complex is directly involved in the immune response, and thus the genes coding for its proteins are useful markers for the study of genetic diversity, susceptibility to disease (autoimmunity and infections), transplant medicine, and pharmacogenetics, among others. The polymorphism of the system also allows researchers to use it as a proxy for population genetics analysis, such as genetic admixture and genetic structure. In order to determine the immunogenetic characteristics of a sample from the northern part of Mexico City and to use them to analyze the genetic differentiation from other admixed populations, including those from previous studies of Mexico City population, we analyzed molecular typing results of donors and patients from the Histocompatibility Laboratory of the Central Blood Bank of the Centro Médico Nacional La Raza selected according to their geographic origin...
July 2017: Human Biology
https://www.readbyqxmd.com/read/29742815/ablation-of-proliferating-neural-stem-cells-during-early-life-is-sufficient-to-reduce-adult-hippocampal-neurogenesis
#12
Mary Youssef, Varsha S Krish, Greer S Kirshenbaum, Piray Atsak, Tamara J Lass, Sophie R Lieberman, E David Leonardo, Alex Dranovsky
Environmental exposures during early life, but not during adolescence or adulthood, lead to persistent reductions in neurogenesis in the adult hippocampal dentate gyrus (DG). The mechanisms by which early life exposures lead to long-term deficits in neurogenesis remain unclear. Here, we investigated whether targeted ablation of dividing neural stem cells during early life is sufficient to produce long-term decreases in DG neurogenesis. Having previously found that the stem cell lineage is resistant to long-term effects of transient ablation of dividing stem cells during adolescence or adulthood (Kirshenbaum et al...
May 9, 2018: Hippocampus
https://www.readbyqxmd.com/read/29742109/effect-of-single-dose-imipramine-on-chronic-low-back-and-experimental-pain-a-randomized-controlled-trial
#13
Jürg Schliessbach, Andreas Siegenthaler, Lukas Bütikofer, Andreas Limacher, Peter Juni, Pascal H Vuilleumier, Ulrike Stamer, Lars Arendt-Nielsen, Michele Curatolo
Antidepressants are frequently prescribed as co-analgesics in chronic pain. While their efficacy is well documented for neuropathic pain, the evidence is less clear in musculoskeletal pain conditions. The present study therefore evaluated the effect of the tricyclic antidepressant imipramine on chronic low-back pain in a randomized, double-blinded placebo-controlled design. To explore the mechanisms of action and the influence of drug metabolism, multimodal quantitative sensory tests (QST) and genotyping for cytochrome P450 2D6 (CYP2D6) were additionally performed...
2018: PloS One
https://www.readbyqxmd.com/read/29738309/pharmacogenetic-testing-by-polymorphic-markers-681g-a-and-636g-a-cyp2c19-gene-in-patients-with-acute-coronary-syndrome-and-gastric-ulcer-in-the-republic-of-sakha-yakutia
#14
Denis S Fedorinov, Karin B Mirzaev, Dmitriy V Ivashchenko, Ilyas I Temirbulatov, Dmitriy A Sychev, Nadezda R Maksimova, Jana V Chertovskih, Nyurguiana V Popova, Ksenia S Tayurskaya, Zoya A Rudykh
BACKGROUND: The focus of the study is to determine the prevalence of CYP2C19 alleles, associated with the risk of changes in the pharmacological response to clopidogrel and proton pump inhibitors in patients with acute coronary syndrome (ACS) and gastric ulcer from Russian and Yakut ethnic groups. METHODS: The research included 411 patients with ACS (143 Russians and 268 Yakuts) and 204 patients with histologically confirmed gastric ulcer (63 Russians and 141 Yakuts)...
May 8, 2018: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/29734517/rosuvastatin-induced-rhabdomyolysis-possible-role-of-ticagrelor-and-patients-pharmacogenetic-profile
#15
Majda Vrkić Kirhmajer, Viola Macolić Šarinić, Livija Šimičević, Iva Ladić, Krešimir Putarek, Ljiljana Banfić, Nada Božina
Up to the beginning of 2018, a total of eight cases describing rare but clinically important drug interactions between rosuvastatin and ticagrelor which resulted in rhabdomyolysis have been noted in the Global World Health Organization (WHO) adverse drug reaction (ADR) database (VigiBase) as well as in available literature. There are several possible factors which could contribute to the onset of rhabdomyolysis: old age, initially excessive rosuvastatin dose, drug-drug interactions (DDI) on metabolic enzymes (CYPs and UGTs) and drug transporter levels (ABCB1, ABCG2, OATP1B1) and pharmacogenetic predisposition...
May 7, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29734486/pharmacogenetic-testing-among-patients-with-mood-and-anxiety-disorders-is-associated-with-decreased-utilization-and-cost-a-propensity-score-matched-study
#16
Roy H Perlis, Rajesh Mehta, Alison M Edwards, Arun Tiwari, Guido W Imbens
BACKGROUND: Naturalistic and small randomized trials have suggested that pharmacogenetic testing may improve treatment outcomes in depression, but its cost-effectiveness is not known. There is growing enthusiasm for personalized medicine, relying on genetic variation as a contributor to heterogeneity of treatment effects. We sought to examine the relationship between a commercial pharmacogenetic test for psychotropic medications and 6-month cost of care and utilization in a large commercial health plan...
May 7, 2018: Depression and Anxiety
https://www.readbyqxmd.com/read/29733708/horizon-scan-of-clinical-laboratories-offering-pharmacogenetic-testing
#17
Susanne B Haga, Ariel Kantor
Pharmacogenetic (PGx) testing involves the analysis of genes known to affect response to medications. The field has been projected as a leading application of personalized or precision medicine, but the use of PGx tests has been stymied, in part, by the lack of clinical evidence of utility and reported low provider awareness. Another factor is the availability of testing. The range and types of PGx tests available have not been assessed to date. In the period September 2017-January 2018 we analyzed the numbers and types of PGx tests offered by clinical testing laboratories in the US...
May 2018: Health Affairs
https://www.readbyqxmd.com/read/29731739/single-gene-congenic-strain-reveals-the-effect-of-zbtb16-on-dexamethasone-induced-insulin-resistance
#18
Michaela Krupková, František Liška, Ludmila Kazdová, Lucie Šedová, Adéla Kábelová, Drahomíra Křenová, Vladimír Křen, Ondřej Šeda
Background: Glucocorticoids (GCs) are potent therapeutic agents frequently used for treatment of number of conditions, including hematologic, inflammatory, and allergic diseases. Both their therapeutic and adverse effects display significant interindividual variation, partially attributable to genetic factors. We have previously isolated a seven-gene region of rat chromosome 8 sensitizing to dexamethasone (DEX)-induced dyslipidemia and insulin resistance (IR) of skeletal muscle. Using two newly derived congenic strains, we aimed to investigate the effect of one of the prime candidates for this pharmacogenetic interaction, the Zbtb16 gene...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29731658/budget-impact-model-for-oncopharmacogenetics-from-the-perspective-of-mandatory-basic-health-insurance-in-switzerland-using-the-example-of-breast-cancer
#19
Thomas D Szucs, Kevin P Szillat, Eva Blozik
Single-nucleotide polymorphisms (SNPs) can severely impact individual drug response and health outcomes in cancer patients. Genetic tests to screen for marker SNPs are available to adjust the drug dose of oncologicals to the patient's needs. However, it is unclear whether the positive effects outbalance the increased costs or even lead to an overall cost reduction. This very pragmatic analysis used three frequently used oncologicals for the treatment of breast cancer to evaluate whether preemptive pharmacogenetic testing may have a cost-reducing impact on health care spending in the Swiss health care system...
2018: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/29728861/patient-characteristics-driving-clinical-utility-in-psychiatric-pharmacogenetics-a-reanalysis-from-the-ab-gen-multicentric-trial
#20
J M Menchón, J Espadaler, M Tuson, J Saiz-Ruiz, J Bobes, E Vieta, E Álvarez, V Pérez
Clinical utility of commercial multi-gene pharmacogenetic tests in depression is starting to be studied with some promising results on efficacy and tolerability. Among the next steps is the definition of the patient profile that is most likely to benefit from testing. Here we present a reanalysis of data from the AB-GEN randomized clinical trial showing that clinical utility of pharmacogenetic testing can be markedly influenced by patient characteristics such as age, baseline severity and duration of current depressive episode...
May 4, 2018: Journal of Neural Transmission
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