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https://www.readbyqxmd.com/read/28229376/the-pharmacogenetics-of-tacrolimus-in-corticosteroid-sparse-pediatric-and-adult-kidney-transplant-recipients
#1
Mads Juul Madsen, Troels K Bergmann, Kim Brøsen, Helle Charlotte Thiesson
INTRODUCTION: Tacrolimus is a calcineurin inhibitor used as an immunosuppressant drug in solid organ transplantation, and is mainly metabolized by cytochrome P450 (CYP) 3A4 and CYP3A5. Studies have shown an association between the CYP3A5 genotype and tacrolimus dose-adjusted trough concentrations. Variants in the genes PPARA, POR and CYP3A4 have recently been shown to influence tacrolimus metabolism. Furthermore, pharmacokinetic interaction between corticosteroid treatment and tacrolimus has been shown...
February 22, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28220511/review-article-pharmacotherapy-for-alcohol-dependence-the-why-the-what-and-the-wherefore
#2
REVIEW
E T Goh, M Y Morgan
BACKGROUND: The development of alcohol dependence is associated with significant morbidity and mortality. For the majority of affected people the most appropriate goal, in terms of drinking behaviour, is abstinence from alcohol. Psychosocial intervention is the mainstay of the treatment but adjuvant pharmacotherapy is also available and its use recommended. AIM: To provide an updated analysis of current and potential pharmacotherapeutic options for the management of alcohol dependence...
February 20, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28210634/potential-of-a-pharmacogenetic-guided-algorithm-to-predict-optimal-warfarin-dosing-in-a-high-risk-hispanic-patient-role-of-a-novel-nqo1-2-polymorphism
#3
Dagmar F Hernandez-Suarez, Karla Claudio-Campos, Javier E Mirabal-Arroyo, Bianca A Torres-Hernández, Angel López-Candales, Kyle Melin, Jorge Duconge
Deep abdominal vein thrombosis is extremely rare among thrombotic events secondary to the use of contraceptives. A case to illustrate the clinical utility of ethno-specific pharmacogenetic testing in warfarin management of a Hispanic patient is reported. A 37-year-old Hispanic Puerto Rican, non-gravid female with past medical history of abnormal uterine bleeding on hormonal contraceptive therapy was evaluated for abdominal pain. Physical exam was remarkable for unspecific diffuse abdominal tenderness, and general initial laboratory results-including coagulation parameters-were unremarkable...
October 2016: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28207934/role-of-hla-c-06-in-clinical-response-to-ustekinumab-evidence-from-real-life-in-a-large-cohort-of-european-patients
#4
M Talamonti, M Galluzzo, J M van den Reek, E M de Jong, J L W Lambert, P Malagoli, L Bianchi, A Costanzo
BACKGROUND: Little is known about role of HLA-C*06 related to response to psoriasis treatments. OBJECTIVES: This study that involved four European centres aims to confirm the role of HLA-C*06 in a new large cohort of patients, as a pharmacogenetic marker of response to ustekinumab. METHODS: In this retrospective multicenter study we reviewed data of 255 psoriasis patients genotyped for HLA-C*06, which have started ustekinumab treatment between January 2014 and March 2015...
February 16, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28206966/impact-of-dna-repair-gene-polymorphisms-on-the-risk-of-biochemical-recurrence-after-radiotherapy-and-overall-survival-in-prostate-cancer
#5
Chiara Zanusso, Roberto Bortolus, Eva Dreussi, Jerry Polesel, Marcella Montico, Erika Cecchin, Sara Gagno, Flavio Rizzolio, Mauro Arcicasa, Giacomo Novara, Giuseppe Toffoli
The identification of biomarkers of biochemical recurrence (BCR) in prostate cancer (PCa) patients undergoing radiotherapy (RT) represents an unanswered clinical issue. The primary aim of this study was the definition of new genetic prognostic biomarkers in DNA repair genes (DRGs), considering both BCR and overall survival (OS) as clinical end-points. The secondary aim was to explore the potential clinical impact of these genetic variants with the decision curve analysis (DCA) and the sensitivity analysis.We analyzed 22 germline polymorphisms in 14 DRGs on 542 Caucasian PCa patients treated with RT as primary therapy...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28203102/the-hla-a-31-01-allele-influence-on-carbamazepine-treatment
#6
REVIEW
Vincent Lai Ming Yip, Munir Pirmohamed
Carbamazepine (CBZ) is an effective anticonvulsant that can sometimes cause hypersensitivity reactions that vary in frequency and severity. Strong associations have been reported between specific human leukocyte antigen (HLA) alleles and susceptibility to CBZ hypersensitivity reactions. Screening for HLA-B*15:02 is mandated in patients from South East Asia because of a strong association with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). HLA-A*31:01 predisposes to multiple phenotypes of CBZ hypersensitivity including maculopapular exanthema, hypersensitivity syndrome, and SJS/TEN in a range of populations including Europeans, Japanese, South Koreans and Han Chinese, although the effect size varies between the different phenotypes and populations...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28198005/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-pharmacogenetics-guided-warfarin-dosing-2017-update
#7
Julie A Johnson, Kelly E Caudle, Li Gong, Michelle Whirl-Carrillo, C Michael Stein, Stuart A Scott, Ming Ta Michael Lee, Brian F Gage, Stephen E Kimmel, Minoli A Perera, Jeffrey L Anderson, Munir Pirmohamed, Teri E Klein, Nita A Limdi, Larisa H Cavallari, Mia Wadelius
This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype-guided warfarin dosing to achieve a target international normalized ratio of 2-3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry...
February 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28188737/genetic-variation-in-the-behavioral-effects-of-buprenorphine-in-female-mice-derived-from-a-murine-model-of-the-oprm1-a118g-polymorphism
#8
Caroline A Browne, Rebecca L Erickson, Julie A Blendy, Irwin Lucki
Pharmacogenetic studies have identified the non-synonymous single nucleotide polymorphism (A118G) in the human mu opioid receptor (MOR) gene (OPRM1) as a critical genetic variant capable of altering the efficacy of opioid therapeutics. To date few studies have explored the potential impact of the OPRM1 A118G polymorphism on the pharmacological effects of buprenorphine (BPN), a potent MOR partial agonist and kappa opioid receptor antagonist, which is approved by the FDA for the treatment of opioid addiction and chronic pain...
February 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28187506/the-effect-of-gene-variants-on-levonorgestrel-pharmacokinetics-when-combined-with-antiretroviral-therapy-containing-efavirenz-or-nevirapine
#9
M Neary, M Lamorde, A Olagunju, K M Darin, C Merry, P Byakika-Kibwika, D J Back, M Siccardi, A Owen, K K Scarsi
Reduced levonorgestrel concentrations from the levonorgestrel contraceptive implant was previously seen when given concomitantly with efavirenz. We sought to assess whether single nucleotide polymorphisms (SNPs) in genes involved in efavirenz and nevirapine metabolism were linked to these changes in levonorgestrel concentration. SNPs in CYP2B6, CYP2A6, NR1I2 and NR1I3 were analysed. Associations of participant demographics and genotype with levonorgestrel pharmacokinetics were evaluated in HIV-positive women using the levonorgestrel implant plus efavirenz- or nevirapine-based ART, in comparison to ART-naïve women using multivariate linear regression...
February 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28183252/pharmacological-profile-and-pharmacogenomics-of-anti-cancer-drugs-used-for-targeted-therapy
#10
Raffaele Di Francia, Angela De Monaco, Mariangela Saggese, Giancarla Iaccarino, Stefania Crisci, Ferdinando Frigeri, Rosaria De Filippi, Massimiliano Berretta, Antonio Pinto
Drugs for targeted therapies are primarily Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA molecules and microRNA. The use of these new agents generates a multifaceted step in the pharmacokinetics (PK) of these drugs. Individual PK variability is often large, and unpredictability observed in the response to the pharmacogenetic profile of the patient (e.g. cytochome P450 enzyme), patient characteristics such as adherence to treatment and environmental factors. Objective This review aims to overview the latest anticancer drugs eligible for targeted therapies and the most recent finding in pharmacogenomics related to toxicity/resistance because either individual gene polymorphisms or acquired mutation in a cancer cell...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28178974/antidepressant-prescribing-in-the-precision-medicine-era-a-prescriber-s-primer-on-pharmacogenetic-tools
#11
REVIEW
Chad A Bousman, Malcolm Forbes, Mahesh Jayaram, Harris Eyre, Charles F Reynolds, Michael Berk, Malcolm Hopwood, Chee Ng
About half of people who take antidepressants do not respond and many experience adverse effects. These detrimental outcomes are in part a result of the impact of an individual's genetic profile on pharmacokinetics and pharmcodynamics. If known and made available to clinicians, this could improve decision-making and antidepressant therapy outcomes. This has spurred the development of numerous pharmacogenetic-based decision support tools. In this article, we provide an overview of pharmacogenetic decision support tools, with particular focus on tools relevant to antidepressants...
February 8, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28176850/application-of-machine-learning-models-to-predict-tacrolimus-stable-dose-in-renal-transplant-recipients
#12
Jie Tang, Rong Liu, Yue-Li Zhang, Mou-Ze Liu, Yong-Fang Hu, Ming-Jie Shao, Li-Jun Zhu, Hua-Wen Xin, Gui-Wen Feng, Wen-Jun Shang, Xiang-Guang Meng, Li-Rong Zhang, Ying-Zi Ming, Wei Zhang
Tacrolimus has a narrow therapeutic window and considerable variability in clinical use. Our goal was to compare the performance of multiple linear regression (MLR) and eight machine learning techniques in pharmacogenetic algorithm-based prediction of tacrolimus stable dose (TSD) in a large Chinese cohort. A total of 1,045 renal transplant patients were recruited, 80% of which were randomly selected as the "derivation cohort" to develop dose-prediction algorithm, while the remaining 20% constituted the "validation cohort" to test the final selected algorithm...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28176639/personalized-medicine-in-the-paediatric-population-the-balance-between-pharmacogenetics-progress-and-bioethics
#13
Stefania Schiavone, Margherita Neri, Cristoforo Pomara, Irene Riezzo, Luigia Trabace, Emanuela Turillazzi
Personalized medicine (PM) is becoming increasingly important in contemporary clinical and research scenarios. In the context of PM, pharmacogenomics and pharmacogenetics are aimed at the genetic personalization of drug response. Extrinsic and intrinsic factors may explain inter-individual variability in drug response. Among such factors, age seems to specifically intervene to modulate drug response since normal developmental changes may influence the exposure-response relation. Consequently, the potential benefit of pharmacogenomics (PGx) in the paediatric population is considerable...
February 7, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28176638/personalized-medicine-and-adverse-drug-reactions-the-experience-of-an-italian-teaching-hospital
#14
Raffaele La Russa, Vittorio Fineschi, Mariantonia Di Sanzo, Vittorio Gatto, Alessandro Santurro, Gabriella Martini, Matteo Scopetti, Paola Frati
The personalized medicine is a model of medicine based on inherent difference given by the genetic heritage that characterizes us, diversity that can affect also our response to administered therapy. Nowadays, the term "adverse drug reaction" is identified with any harmful effect involuntary resulting from the use of a medicinal product; pharmacogenomics, in this field, has the aim to improve the drug response and to reduce the adverse reaction. We analyzed all reports of adverse reaction collected in the Pharmacovigilance Centre database of an Italian University Hospital, at the Sant'Andrea Hospital Sapienza University of Rome, in a period of two years...
February 7, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28165634/pharmacogenetics-of-antiepileptic-drug-efficacy-in-childhood-absence-epilepsy
#15
Tracy A Glauser, Katherine Holland, Valerie P O'Brien, Mehdi Keddache, Lisa J Martin, Peggy O Clark, Avital Cnaan, Dennis Dlugos, Deborah G Hirtz, Shlomo Shinnar, Gregory Grabowski
OBJECTIVE: Determine if common polymorphisms in CACNA1G, CACNA1H, CACNA1I, and ABCB1 are associated with differential short term seizure outcome in Childhood Absence Epilepsy (CAE). METHODS: 446 CAE children in a randomized double blind trial of ethosuximide, lamotrigine and valproate had short term seizure outcome determined. Associations between polymorphisms (minor allele frequency ≥15%) in four genes and seizure outcomes were assessed. In vitro electrophysiology on transfected CACNA1H channels determined impact of one variant on T-type calcium channel responsiveness to ethosuximide...
February 6, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28162244/pharmacogenetics-of-hypersensitivity-drug-reactions
#16
Simone Negrini, Laurent Becquemont
Adverse drug reactions are a significant cause of morbidity and mortality and represent a major burden on the healthcare system. Some of those reactions are immunologically mediated (hypersensitivity reactions) and can be clinically subdivided into two categories: immediate reactions (IgE-related) and delayed reactions (T-cell-mediated). Delayed hypersensitivity reactions include both systemic syndromes and organ-specific toxicities and can be triggered by a wide range of chemically diverse drugs. Recent studies have demonstrated a strong genetic association between human leukocyte antigen alleles and susceptibility to delayed drug hypersensitivity...
January 3, 2017: Thérapie
https://www.readbyqxmd.com/read/28161754/further-characterization-of-the-glyt-1-inhibitor-org25935-anti-alcohol-neurobehavioral-and-gene-expression-effects
#17
Helga Höifödt Lidö, Susanne Jonsson, Petri Hyytiä, Mia Ericson, Bo Söderpalm
The glycine transporter-1 inhibitor Org25935 is a promising candidate in a treatment concept for alcohol use disorder targeting the glycine system. Org25935 inhibits ethanol-induced dopamine elevation in brain reward regions and reduces ethanol intake in Wistar rats. This study aimed to further characterise the compound and used ethanol consumption, behavioral measures, and gene expression as parameters to investigate the effects in Wistar rats and, as pharmacogenetic comparison, Alko-Alcohol (AA) rats. Animals were provided limited access to ethanol in a two-bottle free-choice paradigm with daily drug administration...
February 4, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28160554/pharmacogenetics-of-dipeptidyl-peptidase-4-inhibitors-in-a-taiwanese-population-with-type-2-diabetes
#18
Wen-Ling Liao, Wen-Jane Lee, Ching-Chu Chen, Chieh Hsiang Lu, Chien-Hsiun Chen, Yi-Chun Chou, I-Te Lee, Wayne H-H Sheu, Jer-Yuarn Wu, Chi-Fan Yang, Chung-Hsing Wang, Fuu-Jen Tsai
Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral anti-hyperglycemic drugs enabling effective glycemic control in type 2 diabetes (T2D). Despite DPP-4 inhibitors' advantages, the patients' therapeutic response varies. In this retrospective cohort study, 171 Taiwanese patients with T2D were classified as sensitive or resistant to treatment based on the mean change in HbA1c levels. Using an assumption-free genome-wide association study, 45 single nucleotide polymorphisms (SNPs) involved in the therapeutic response to DPP-4 inhibitors (P < 1 × 10-4) were identified at or near PRKD1, CNTN3, ASK, and LOC10537792...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28159590/pharmacogenetics-of-antidepressant-response-a-polygenic-approach
#19
Judit García-González, Katherine E Tansey, Joanna Hauser, Neven Henigsberg, Wolfgang Maier, Ole Mors, Anna Placentino, Marcella Rietschel, Daniel Souery, Tina Žagar, Piotr M Czerski, Borut Jerman, Henriette N Buttenschøn, Thomas G Schulze, Astrid Zobel, Anne Farmer, Katherine J Aitchison, Ian Craig, Peter McGuffin, Michel Giupponi, Nader Perroud, Guido Bondolfi, David Evans, Michael O'Donovan, Tim J Peters, Jens R Wendland, Glyn Lewis, Shitij Kapur, Roy Perlis, Volker Arolt, Katharina Domschke, Gerome Breen, Charles Curtis, Lee Sang-Hyuk, Carol Kan, Stephen Newhouse, Hamel Patel, Bernhard T Baune, Rudolf Uher, Cathryn M Lewis, Chiara Fabbri
BACKGROUND: Major depressive disorder (MDD) has a high personal and socio-economic burden and >60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait. METHODS: Polygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy; 2) its overlap with MDD and schizophrenia...
January 31, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28154241/stellate-cells-drive-maturation-of-the-entorhinal-hippocampal-circuit
#20
Flavio Donato, R Irene Jacobsen, May-Britt Moser, Edvard I Moser
The neural representation of space relies on a network of entorhinal-hippocampal cell types with firing patterns tuned to different abstract features of the environment. To determine how this network is set up during early postnatal development, we monitored markers of structural maturation in developing mice, both in naïve animals and after temporally restricted pharmacogenetic silencing of specific cell populations. We found that entorhinal stellate cells provide an activity-dependent instructive signal that drives maturation sequentially and unidirectionally through the intrinsic circuits of the entorhinal-hippocampal network The findings raise the possibility that a small number of autonomously developing neuronal populations operate as intrinsic drivers of maturation across widespread regions of cortex...
February 2, 2017: Science
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