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Pharmacogenetic

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https://www.readbyqxmd.com/read/28440827/molecular-dynamics-investigations-of-membrane-bound-cyp2c19-polymorphisms-reveal-distinct-mechanisms-for-peripheral-variants-by-long-range-effects-on-the-enzymatic-activity
#1
Ying-Lu Cui, Rong-Ling Wu
Increasing sophistication in methods used to account for human polymorphisms in susceptibility to drug metabolism has been one of the success stories in the prevention of adverse drug reactions. Genetic polymorphisms in drug-metabolizing enzymes can affect enzyme activity and cause differences in treatment response or drug toxicity. CYP2C19 is one of the most highly polymorphic CYP enzymes and acts on 10-15% of drugs in current clinical use. Despite the number of experimental analyses carried out for this system, the detailed structural basis for altered catalytic properties of polymorphic CYP2C19 variants remains unexplained at the atomic level...
April 25, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28440343/cyp3a4-genotype-is-associated-with-sildenafil-concentrations-in-patients-with-heart-failure-with-preserved-ejection-fraction
#2
S de Denus, J L Rouleau, D L Mann, G S Huggins, N L Pereira, S H Shah, T P Cappola, R Fouodjio, I Mongrain, M-P Dubé
Despite its established inter-individual variability, sildenafil has been the subject of only a few pharmacogenetic investigations, with limited data regarding the genetic modulators of its pharmacokinetics. We conducted a pharmacogenetic sub-study of patients randomized to sildenafil (n=85) in the RELAX trial, which investigated the impact of high-dose sildenafil in patients with heart failure with preserved left ventricular ejection fraction (HFpEF). In the overall population, the CYP3A4 inferred phenotype appeared associated with the dose-adjusted peak concentrations of sildenafil at week 12 and week 24 (adjusted P=0...
April 25, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28439573/systematic-review-of-cyclosporin-a-induced-%C3%A2-gingival-overgrowth-and-genetic-predisposition
#3
Georgios S Chatzopoulos, Vasiliki P Koidou, Larry F Wolff
OBJECTIVE: This systematic review aimed to investigate the influence of gene polymorphisms on the development of gingival overgrowth in renal transplant patients treated with cyclosporin A. METHOD AND MATERIALS: Electronic and hand literature searches were conducted by two independent reviewers in MEDLINE-Pubmed, Cochrane Library, ISI Web of Science, and SCOPUS Elsevier for prospective (case-control studies, cohort studies), cross-sectional, and retrospective studies published up to June 2016 (first week) in any language...
April 24, 2017: Quintessence International
https://www.readbyqxmd.com/read/28435307/comparison-of-cyp2c9-cyp2c19-cyp2d6-abcb1-and-slco1b1-gene-polymorphism-frequency-in-russian-and-nanai-populations
#4
Dmitrij Alekseevitch Sychev, Grigorij Nikolaevich Shuev, Salavat Shejhovich Suleymanov, Kristina Anatol'evna Ryzhikova, Karin Badavievich Mirzaev, Elena Anatol'evna Grishina, Natalia Evgenievna Snalina, Zhannet Alimovna Sozaeva, Anton Mikhailovich Grabuzdov, Irina Andreevna Matsneva
BACKGROUND: The efficiency and safety of drug therapy depends on the peculiarities of functioning of the P450 cytochrome group and transporting proteins. There are significant differences for single-nucleotide polymorphism (SNP) frequency. MATERIALS AND METHODS: We studied the peculiarities of P450 cytochrome polymorphisms, SLCO1B1 transporting protein, and P-glycoprotein carriage in healthy volunteers in the Nanai ethnic group living in Russia, and compared them to the carriage of SNPs in the Russian population according to literature data...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28431457/precision-medicine-and-pharmacogenetics-what-does-oncology-have-that-addiction-medicine-does-not
#5
Henry R Kranzler, Rachel V Smith, Robert Schnoll, Afaf Moustafa, Emma Greenstreet-Akman
BACKGROUND AND AIMS: Precision, personalized or stratified medicine, which promises to deliver the right treatment to the right patient, is a topic of international interest in both the lay press and the scientific literature. A key aspect of precision medicine is the identification of biomarkers that predict the response to medications (i.e. pharmacogenetics). We examined why, despite the great strides that have been made in biomarker identification in many areas of medicine, only in oncology has there been substantial progress in their clinical implementation...
April 21, 2017: Addiction
https://www.readbyqxmd.com/read/28430649/abcg2-and-ncf4-polymorphisms-are-associated-with-clinical-outcomes-in-diffuse-large-b-cell-lymphoma-patients-treated-with-r-chop
#6
Duo Liu, Nan Wu, Haiming Sun, Mei Dong, Tianzhu Guo, Peng Chi, Guofu Li, Donglin Sun, Yan Jin
The impact of pharmacogenetics on predicting survival in diffuse large B-cell lymphoma (DLBCL) remains unclear. We tested 337 DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 9 single nucleotide polymorphisms from 6 genes (CD20, FCGR2A, NAD(P)H, ABCC2, ABCG2 and CYP3A5). Patients who carried the NCF4 rs1883112 GG genotype showed significantly shorter progression-free survival (PFS) (P = 0.023) and event-free survival (EFS) (P < 0.001) comparing with A allele...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430339/characterization-of-a-rare-nonpathogenic-sequence-variant-c-1905c-t-of-the-dihydropyrimidine-dehydrogenase-gene-dpyd
#7
Raffaele Palmirotta, Domenica Lovero, Erica Silvestris, Claudia Carella, Claudia Felici, Davide Quaresmini, Paola Cafforio, Franco Silvestris
BACKGROUND: In the era of precision medicine, the suitability of fluoropyrimidine therapies in clinical oncology can be checked by pharmacogenetic investigations of single patients, thus optimizing resources and indicating the appropriate drugs to personalize their chemotherapy. For example, the presence of dihydropyrimidine dehydrogenase gene (DPYD) polymorphisms in cancer patients may lead to adverse effects when adopting fluoropyrimidine-based therapies. METHODS: We detected in a cancer patient a rare germline synonymous heterozygous variant of DPYD (c...
April 11, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28427087/pretreatment-serum-uracil-concentration-as-a-predictor-of-severe-and-fatal-fluoropyrimidine-associated-toxicity
#8
Didier Meulendijks, Linda M Henricks, Bart A W Jacobs, Abidin Aliev, Maarten J Deenen, Niels de Vries, Hilde Rosing, Erik van Werkhoven, Anthonius de Boer, Jos H Beijnen, Caroline M P W Mandigers, Marcel Soesan, Annemieke Cats, Jan H M Schellens
BACKGROUND: We investigated the predictive value of dihydropyrimidine dehydrogenase (DPD) phenotype, measured as pretreatment serum uracil and dihydrouracil concentrations, for severe as well as fatal fluoropyrimidine-associated toxicity in 550 patients treated previously with fluoropyrimidines during a prospective multicenter study. METHODS: Pretreatment serum concentrations of uracil and dihydrouracil were measured using a validated LC-MS/MS method. The primary endpoint of this analysis was global (any) severe fluoropyrimidine-associated toxicity, that is, grade ⩾3 toxicity according to the NCI CTC-AE v3...
April 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28422153/clinical-pharmacogenetic-models-for-personalized-cancer-treatment-application-to-malignant-mesothelioma
#9
Katja Goričar, Viljem Kovač, Vita Dolžan
Large interindividual differences in treatment outcome are observed in cancer patients undergoing chemotherapy. Our aim was to develop and validate clinical-pharmacogenetic prediction models of gemcitabine/cisplatin or pemetrexed/cisplatin treatment outcome and develop an algorithm for genotype-based treatment recommendations in malignant mesothelioma (MM). We genotyped 189 MM patients for polymorphisms in gemcitabine, pemetrexed and cisplatin metabolism, transport and drug target genes and DNA repair pathways...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28421338/tailoring-pharmacotherapy-to-specific-eating-behaviours-in-obesity-can-recommendations-for-personalised-therapy-be-made-from-the-current-data
#10
Carl A Roberts, Paul Christiansen, Jason C G Halford
Pharmacotherapy provides an adjunct to behaviour modification in the management of obesity. There are a number of new drug therapies purportedly targeting appetite; liraglutide, and bupropion/naltrexone, which are European Medicines Agency and US Food and Drug Administration (FDA) approved, and lorcaserin and phentermine/topiramate, which have FDA approval only. Each of the six drugs, used singly or in combination, has distinct pharmacological, and presumably distinct behavioural, mechanisms of action, thus the potential to provide defined therapeutic options to personalise the management of obesity...
April 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28421156/the-personalization-of-clopidogrel-antiplatelet-therapy-the-role-of-integrative-pharmacogenetics-and-pharmacometabolomics
#11
REVIEW
Arwa M Amin, Lim Sheau Chin, Dzul Azri Mohamed Noor, Muhamad Ali Sk Abdul Kader, Yuen Kah Hay, Baharudin Ibrahim
Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing...
2017: Cardiology Research and Practice
https://www.readbyqxmd.com/read/28420875/down-regulation-of-cholinergic-signaling-in-the-habenula-induces-anhedonia-like-behavior
#12
Seungrie Han, Soo Hyun Yang, Jin Yong Kim, Seojung Mo, Esther Yang, Ki Myung Song, Byung-Joo Ham, Naguib Mechawar, Gustavo Turecki, Hyun Woo Lee, Hyun Kim
Dysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression levels of cholinergic signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated in a chronic restraint stress (CRS) rat model of depression, in which rats display depression-like behaviors such as anhedonia and mood despair...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28414390/therapeutic-monitoring-of-amiodarone-pharmacokinetics-and-evaluation-of-the-relationship-between-effect-and-dose-concentration
#13
Erika Hrudikova Vyskocilova, Milan Grundmann, Jana Duricova, Ivana Kacirova
Amiodarone is the most effective agent in the therapy of arrhythmias. However, the clinical effect of acute and chronic treatment is unclear and there are differences irrespective of comparable plasma/myocardial amiodarone and its metabolite desethylamiodarone concentations as well. Its unusual pharmacokinetics results in interindividual variation in plasma levels. The association between amiodarone and desethylamiodarone plasma levels and clinical efficacy is difficult to evaluate. This review was carried out to assess whether there is any objective correlation between amiodarone and desethylamiodarone plasma levels and the clinical effect...
March 31, 2017: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/28414282/-pharmacometabonomics-the-novel-way-to-personalized-drug-therapy
#14
REVIEW
D L Maslov, E E Balashova, P G Lokhov, A I Archakov
The review is devoted to pharmacometabonomics - a new branch of science focused on personalization of drug therapy through the comprehensive analysis of metabolites of patient's biological fluids. It considers the history of pharmacometabonomic, positioning to other "-omic" sciences, and system approach, realized by this science, in determination of individual therapeutic dose of the drugs and also a technical implementation of pharmacometabonomic based on direct mass spectrometry of blood plasma metabolites...
March 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28414144/intestinal-drug-interactions-mediated-by-oatps-a-systematic-review-of-pre-clinical-and-clinical-findings
#15
REVIEW
Jingjing Yu, Zhu Zhou, Jessica Tay-Sontheimer, René H Levy, Isabelle Ragueneau-Majlessi
In recent years, an increasing number of clinical drug-drug interactions (DDIs) have been attributed to inhibition of intestinal organic anion transporting polypeptides (OATPs); however, only a few of these DDI results were reflected in drug labels. This review aims to provide a thorough analysis of intestinal OATP-mediated pharmacokinetic-based DDIs, using both in vitro and clinical investigations, highlighting the main mechanistic findings and discussing their clinical relevance. On the basis of pharmacogenetic and clinical DDI results, a total of 12 drugs were identified as possible clinical substrates of OATP2B1 and/or OATP1A2...
April 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28410576/knowledge-and-attitude-regarding-pharmacogenetics-among-formerly-pregnant-women-in-the-netherlands-and-their-interest-in-pharmacogenetic-research
#16
Aizati N A Daud, Eefke L Bergsma, Jorieke E H Bergman, Hermien E K De Walle, Wilhelmina S Kerstjens-Frederikse, Bert J Bijker, Eelko Hak, Bob Wilffert
BACKGROUND: Pharmacogenetics is an emerging field currently being implemented to improve safety when prescribing drugs. While many women who take drugs during pregnancy would likely benefit from such personalized drug therapy, data is lacking on the awareness towards pharmacogenetics among women. We aim to determine the level of knowledge and acceptance of formerly pregnant women in the Netherlands regarding pharmacogenetics and its implementation, and their interest in pharmacogenetic research...
April 14, 2017: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/28409480/genetic-testing-for-opioid-pain-management-a-primer
#17
Deepti Agarwal, Mercy A Udoji, Andrea Trescot
Patients see their primary care physicians (PCPs) for a variety of medical conditions, chronic pain being one of the most common. An increased use of prescription medications (especially opioids) has led to an increase in adverse drug reactions and has heightened our awareness of the variability in response to medications. Opioids and other pain adjuvants are widely used, and drug-drug interactions involving these analgesics can be problematic and potentially lethal. Pharmacogenetics has improved our understanding of drug efficacy and response, opened doors to individual tailoring of medical management, and created a series of ethical and economic considerations...
April 13, 2017: Pain and Therapy
https://www.readbyqxmd.com/read/28406961/pharmacogenetic-variants-in-tpmt-alter-cellular-responses-to-cisplatin-in-inner-ear-cell-lines
#18
Amit P Bhavsar, Erandika P Gunaretnam, Yuling Li, Jafar S Hasbullah, Bruce C Carleton, Colin J D Ross
Cisplatin is a highly-effective and widely-used chemotherapeutic agent that causes ototoxicity in many patients. Pharmacogenomic studies of key genes controlling drug biotransformation identified variants in thiopurine methyltransferase (TPMT) as predictors of cisplatin-induced ototoxicity, although the mechanistic basis of this interaction has not been reported. Expression constructs of TPMT*3A, *3B and *3C variants were generated and monitored in cultured cells. Cellular TPMT*3A levels were detected at >20-fold lower amounts than the wild type confirming the unstable nature of this variant...
2017: PloS One
https://www.readbyqxmd.com/read/28403774/pharmacogenetics-of-aromatase-inhibitors-in-endocrine-responsive-breast-cancer-lessons-learnt-from-tamoxifen-and-cyp2d6-genotyping
#19
Karin Jeanne Baatjes, Magda Conradie, Justus Paul Apffelstaedt, Maritha Kotze
BACKGROUND: Genetics play a significant role in drug metabolism of endocrine therapy of breast cancer. These aspects have been studied extensively in patients on tamoxifen, but the pharmacogenetics of aromatase inhibitors are less established. In contrast to the protective effect of tamoxifen, aromatase inhibitors are linked with an increased risk for bone loss and fractures. OBJECTIVE: This review outlines key issues around implementation of pharmacogenetics of cytochrome P450 and tamoxifen as a model for optimal use of aromatase inhibitors in postmenopausal women with estrogen receptor positive breast cancer...
April 12, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28400373/association-between-vegf-a-and-vegfr-2-polymorphisms-and-response-to-treatment-of-neovascular-amd-with-anti-vegf-agents-a-meta-analysis
#20
Mingxing Wu, Haibo Xiong, Yan Xu, Xiaojing Xiong, Hongmi Zou, Minming Zheng, Xiuqing Wang, Xiyuan Zhou
AIMS: The purpose of this study is to investigate whether gene polymorphisms of the vascular endothelial growth factor A (VEGF-A) and its receptor (VEGFR-2) have a pharmacogenetics effect on the anti-VEGF treatment for neovascular age-related macular degeneration (nAMD). METHODS: We carried out a meta-analysis focusing on the relationship between VEGF-related gene polymorphisms and treatment response of nAMD. RESULTS: For the single nucleotide polymorphisms (SNPs) within VEGF-A and VEGFR-2, anti-VEGF treatment was much more effective in patients with nAMD having rs833061 (CC vs TT:OR=2...
October 21, 2016: British Journal of Ophthalmology
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