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Pharmacogenomics Journal

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https://read.qxmd.com/read/30760878/correction-polymorphisms-at-phase-i-metabolizing-enzyme-and-hormone-receptor-loci-influence-the-response-to-anti-tnf-therapy-in-rheumatoid-arthritis-patients
#1
Luz M Canet, Jose M Sánchez-Maldonado, Rafael Cáliz, Ana Rodríguez-Ramos, Carmen B Lupiañez, Helena Canhão, Manuel Martínez-Bueno, Alejandro Escudero, Juana Segura-Catena, Signe B Sorensen, Merete L Hetland, María José Soto-Pino, Miguel A Ferrer, Antonio García, Bente Glintborg, Ileana Filipescu, Eva Pérez-Pampin, Alfonso González-Utrilla, Miguel Ángel López Nevot, Pablo Conesa-Zamora, Alfons den Broeder, Salvatore De Vita, Sven Erik Hobe Jacobsen, Eduardo Collantes-Estevez, Luca Quartuccio, Federico Canzian, João E Fonseca, Marieke J H Coenen, Vibeke Andersen, Juan Sainz
The original version of this Article contained an error in the spelling of the author Ana Rodríguez-Ramos, which was incorrectly given as Ana Rodríguez Ramos. This has now been corrected in both the PDF and HTML versions of the Article.
February 14, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30760877/candidate-gene-analyses-for-acute-pain-and-morphine-analgesia-after-pediatric-day-surgery-african-american-versus-european-caucasian-ancestry-and-dose-prediction-limits
#2
Jin Li, Zhi Wei, Jie Zhang, Hakon Hakonarson, Scott D Cook-Sather
Acute pain and opioid analgesia demonstrate inter-individual variability and polygenic influence. In 241 children of African American and 277 of European Caucasian ancestry, we sought to replicate select candidate gene associations with morphine dose and postoperative pain and then to estimate dose prediction limits. Twenty-seven single-nucleotide polymorphisms (SNPs) from nine genes (ABCB1, ARRB2, COMT, DRD2, KCNJ6, MC1R, OPRD1, OPRM1, and UGT2B7) met selection criteria and were analyzed along with TAOK3. Few associations replicated: morphine dose (mcg/kg) in African American children and ABCB1 rs1045642 (A allele, β = -9...
February 14, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30745565/precision-dosing-of-warfarin-open-questions-and-strategies
#3
Xi Li, Dan Li, Ji-Chu Wu, Zhao-Qian Liu, Hong-Hao Zhou, Ji-Ye Yin
Warfarin has a very narrow therapeutic window and obvious interindividual variability in its effects, with many factors contributing to the body's response. Algorithms incorporating multiple genetic, environment and clinical factors have been established to select a precision dose for each patient. A number of randomized controlled trials (RCTs) were conducted to explore whether patients could benefit from these algorithms; however, the results were inconsistent. Some questions remain to be resolved. Recently, new genetic and non-genetic factors have been discovered to contribute to variability in optimal warfarin doses...
February 12, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30713337/patient-provider-communications-about-pharmacogenomic-results-increase-patient-recall-of-medication-changes
#4
Brittany A Borden, Sang Mee Lee, Keith Danahey, Paige Galecki, Linda Patrick-Miller, Mark Siegler, Matthew J Sorrentino, Yasmin Sacro, Andrew M Davis, David T Rubin, Kristen Lipstreuer, Tamar S Polonsky, Rita Nanda, William R Harper, Jay L Koyner, Deborah L Burnet, Walter M Stadler, Robert T Kavitt, David O Meltzer, Mark J Ratain, Peter H O'Donnell
Effective doctor-patient communication is critical for disease management, especially when considering genetic information. We studied patient-provider communications after implementing a point-of-care pharmacogenomic results delivery system to understand whether pharmacogenomic results are discussed and whether medication recall is impacted. Outpatients undergoing preemptive pharmacogenomic testing (cases), non-genotyped controls, and study providers were surveyed from October 2012-May 2017. Patient responses were compared between visits where pharmacogenomic results guided prescribing versus visits where pharmacogenomics did not guide prescribing...
February 11, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30723316/predicting-antidepressant-treatment-outcome-based-on-socioeconomic-status-and-citalopram-dose
#5
Aurelia Viglione, Flavia Chiarotti, Silvia Poggini, Alessandro Giuliani, Igor Branchi
Selective serotonin reuptake inhibitors (SSRIs), the most prescribed antidepressant drugs, have incomplete efficacy and no clear mechanism of action. In addition, no reliable methods to identify patients who will benefit from treatment is available. In this study, we show that citalopram, a commonly used SSRI, produces a dose-dependent amplification of the influence of the environment on mood, making the severity of symptoms dependent on the level of socioeconomic status (SES). As a consequence, based on SES, we were able to predict which patients would show remission following 12 weeks of treatment in the high, but not the low dose group...
February 6, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30723315/variants-in-vincristine-pharmacodynamic-genes-involved-in-neurotoxicity-at-induction-phase-in-the-therapy-of-pediatric-acute-lymphoblastic-leukemia
#6
Idoia Martin-Guerrero, Angela Gutierrez-Camino, Aizpea Echebarria-Barona, Itziar Astigarraga, Nagore Garcia de Andoin, Aurora Navajas, Africa Garcia-Orad
Vincristine is an important drug of acute lymphoblastic leukemia (ALL) treatment protocols that can cause neurotoxicity. Patients treated with LAL/SHOP protocols often suffer from vincristine-related neurotoxicity in early phases of treatment. A genetic variant in CEP72, a gene involved in vincristine pharmacodynamics, was recently associated with neurotoxicity after prolonged vincristine treatment. This association was not replicated in our Spanish population during induction phase. To test the possibility that other variants in genes involved in vincristine pharmacodynamics were associated with vincristine neuropathy in early phases of the treatment, we evaluated the correlation with toxicity of 24 polymorphisms in 9 key genes in a large cohort of 152 Spanish children with B-ALL homogeneously treated...
February 6, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30723314/genetic-polymorphisms-associated-with-reactive-oxygen-species-and-blood-pressure-regulation
#7
Santiago Cuevas, Van Anthony M Villar, Pedro A Jose
Hypertension is the most prevalent cause of cardiovascular disease and kidney failure, but only about 50% of patients achieve adequate blood pressure control, in part, due to inter-individual genetic variations in the response to antihypertensive medication. Significant strides have been made toward the understanding of the role of reactive oxygen species (ROS) in the regulation of the cardiovascular system. However, the role of ROS in human hypertension is still unclear. Polymorphisms of some genes involved in the regulation of ROS production are associated with hypertension, suggesting their potential influence on blood pressure control and response to antihypertensive medication...
February 6, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30723313/dpyd-6-plays-an-important-role-in-fluoropyrimidine-toxicity-in-addition-to-dpyd-2a-and-c-2846a-t-a-comprehensive-analysis-in-1254-patients
#8
Marzia Del Re, Saverio Cinieri, Angela Michelucci, Stefano Salvadori, Fotios Loupakis, Marta Schirripa, Chiara Cremolini, Stefania Crucitta, Cecilia Barbara, Angelo Di Leo, Tiziana Pia Latiano, Filippo Pietrantonio, Samantha Di Donato, Paolo Simi, Alessandro Passardi, Filippo De Braud, Giuseppe Altavilla, Claudio Zamagni, Roberto Bordonaro, Alfredo Butera, Evaristo Maiello, Carmine Pinto, Alfredo Falcone, Valentina Mazzotti, Riccardo Morganti, Romano Danesi
Dihydropyrimidine dehydrogenase (DPYD) is a highly polymorphic gene and classic deficient variants (i.e., c.1236G>A/HapB3, c.1679T>G, c.1905+1G>A and c.2846A>T) are characterized by impaired enzyme activity and risk of severe adverse drug reactions (ADRs) in patients treated with fluoropyrimidines. The identification of poor metabolizers by pre-emptive DPYD screening may reduce the rate of ADRs but many patients with wild-type genotype for classic variants may still display ADRs. Therefore, the search for additional DPYD polymorphisms associated with ADRs may improve the safety of treatment with fluoropyrimidines...
February 6, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30713339/genetic-polymorphisms-in-abcg2-and-cyp1a2-are-associated-with-imatinib-dose-reduction-in-patients-treated-for-gastrointestinal-stromal-tumors
#9
Michiel C Verboom, Jacqueline S L Kloth, Jesse J Swen, Stefan Sleijfer, Anna K L Reyners, Neeltje Steeghs, Ron H J Mathijssen, Hans Gelderblom, Henk-Jan Guchelaar
Imatinib has a mild toxicity profile, although severe adverse events may develop. In this pharmacogenetic pathway analysis the need for dose reduction and cessation of therapy was tested for an association with single nucleotide polymorphisms (SNPs) in genes related to imatinib pharmacology. Retrospective data from 315 patients with a gastrointestinal stromal tumor who received imatinib 400 mg o.d. was associated with 36 SNPs. SNPs that showed a trend in univariate testing were tested in a multivariate model with clinical factors and correction for multiple testing was performed...
February 4, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30713338/is-a-pharmacogenomic-panel-useful-to-estimate-the-risk-of-oxaliplatin-related-neurotoxicity-in-colorectal-cancer-patients
#10
Federico Nichetti, Felicia Stefania Falvella, Rosalba Miceli, Stefania Cheli, Raffaella Gaetano, Giovanni Fucà, Gabriele Infante, Antonia Martinetti, Carlotta Antoniotti, Alfredo Falcone, Maria Di Bartolomeo, Chiara Cremolini, Filippo de Braud, Filippo Pietrantonio
Oxaliplatin-induced peripheral neurotoxicity (OXPN) is a dose-limiting toxicity in colorectal cancer (CRC) patients. Single nucleotide polymorphisms (SNPs) in genes involved in drug transport may lead to higher intracellular oxaliplatin accumulation in the dorsal root ganglia and thus increased risk of OXPN. In this study, a panel of 5 SNPs, namely ABCC2 (-24C > T/rs717620 and c.4544 G > A/rs8187710), ABCG2 (c.421 C > A/rs2231142), ABCB1 (c.3435 C > T/rs1045642) and SLC31A1 (c...
February 4, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30700811/genome-wide-association-study-of-antidepressant-treatment-resistance-in-a-population-based-cohort-using-health-service-prescription-data-and-meta-analysis-with-gendep
#11
Eleanor M Wigmore, Jonathan D Hafferty, Lynsey S Hall, David M Howard, Toni-Kim Clarke, Chiara Fabbri, Cathryn M Lewis, Rudolf Uher, Lauren B Navrady, Mark J Adams, Yanni Zeng, Archie Campbell, Jude Gibson, Pippa A Thomson, Caroline Hayward, Blair H Smith, Lynne J Hocking, Sandosh Padmanabhan, Ian J Deary, David J Porteous, Ole Mors, Manuel Mattheisen, Kristin K Nicodemus, Andrew M McIntosh
Antidepressants demonstrate modest response rates in the treatment of major depressive disorder (MDD). Despite previous genome-wide association studies (GWAS) of antidepressant treatment response, the underlying genetic factors are unknown. Using prescription data in a population and family-based cohort (Generation Scotland: Scottish Family Health Study; GS:SFHS), we sought to define a measure of (a) antidepressant treatment resistance and (b) stages of antidepressant resistance by inferring antidepressant switching as non-response to treatment...
January 31, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30686821/early-modifications-of-circulating-micrornas-levels-in-metastatic-colorectal-cancer-patients-treated-with-regorafenib
#12
Marta Schirripa, Beatrice Borelli, Romina D'Aurizio, Simone Lubrano, Chiara Cremolini, Gemma Zucchelli, Carlotta Antoniotti, Federica Marmorino, Alessandra Anna Prete, Sabina Murgioni, Francesca Bergamo, Vittorina Zagonel, Andrea Tuccoli, Andrea Marranci, Milena Rizzo, Lorena Tedeschi, Letizia Magnoni, Alfredo Falcone, Fotios Loupakis, Laura Poliseno
Biomarkers able to improve the cost/benefit ratio are urgently needed for metastatic colorectal cancer patients that are eligible to receive regorafenib. Here, we measured plasma levels of ten circulating microRNAs (c-miRNAs) and we investigated their early changes during treatment, as well as possible correlation with clinical outcome. Ten literature-selected c-miRNAs were quantified by qRT-PCR on plasma samples collected at baseline (d1) and after 15 days of treatment (d15). C-miRNAs showing significant changes were further analyzed to establish correlations with outcome...
January 28, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30659276/correction-the-influence-of-fcgr2a-and-fcgr3a-polymorphisms-on-the-survival-of-patients-with-recurrent-or-metastatic-squamous-cell-head-and-neck-cancer-treated-with-cetuximab
#13
T Magnes, T Melchardt, C Hufnagl, L Weiss, C Mittermair, D Neureiter, E Klieser, G Rinnerthaler, S Roesch, A Gaggl, R Greil, A Egle
In the abstract and in other parts of the manuscript the authors wrote that the mutation rs396991 causes a valine (V) to phenylalanine (F) substitution at position 157. However, the correct codon number is 158. These errors have not been fixed in the original Article.
January 18, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30651574/the-effect-of-vitamin-d-pathway-genes-and-deferasirox-pharmacogenetics-on-liver-iron-in-thalassaemia-major-patients
#14
Sarah Allegra, Jessica Cusato, Silvia De Francia, Filomena Longo, Elisa Pirro, Davide Massano, Valeria Avataneo, Amedeo De Nicolò, Antonio Piga, Antonio D'Avolio
Monitoring and treating iron overload is crucial in transfusion-dependent thalassaemia patients. Liver stiffness measurement by transient elastography and T2* magnetic resonance imaging represent non-invasive ways to evaluate the adequacy of the iron chelation treatment. We explored the role of single nucleotide polymorphisms involved in vitamin D metabolism, transport and activity, and in deferasirox metabolism on liver iron burden parameters. One-hundred and five beta-thalassaemia patients, treated with deferasirox, have been enrolled...
January 17, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30651573/prognostic-role-of-genetic-polymorphisms-of-the-interleukin-6-signaling-pathway-in-patients-with-severe-heart-failure
#15
Peter R Hansen, Karl Emil Nelveg-Kristensen, Henrik B Rasmussen, Christian Torp-Pedersen, Lars Køber, Claus Henrik Nielsen, Christian Enevold
Heart failure (HF) is associated with perturbations of the interleukin-6 (IL-6) signaling pathway. A total of 559 Danish subjects with severe chronic HF enrolled in the previously reported Echocardiography and Heart Outcome Study were genotyped for three SNPs in IL6, nine in the IL-6 receptor gene (IL6R), and two in the IL-6 signal transducer gene (IL6ST). After a mean follow-up of 5.0 years, 5 SNPs in IL6R introns (rs12083537, rs6684439, rs4845622, rs4537545, and rs7529229) and a SNP in the IL6R coding region (rs2228145, also known as Asp358Ala) were associated with adverse outcomes, e...
January 17, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30647446/an-economic-model-of-the-cost-utility-of-pre-emptive-genetic-testing-to-support-pharmacotherapy-in-patients-with-major-depression-in-primary-care
#16
Reinier L Sluiter, Joost G E Janzing, Gert Jan van der Wilt, Wietske Kievit, Martina Teichert
The pharmacokinetics of many antidepressants (tricyclic antidepressants (TCA) or selective serotonin re-uptake inhibitors (SSRI)) are influenced by the highly polymorphic CYP2D6 enzyme. Therefore, pharmacogenetics could play an important role in the treatment of depressive patients. The potential cost-utility of screening patients is however still unknown. Therefore, a Markov model was developed to compare the strategy of screening for CYP2D6 and subsequently adjust antidepressant treatment according to a patient's metabolizer profile of poor, extensive, or ultra metabolizer, with the strategy of no screening ('one size fits all' principle)...
January 16, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30647445/warfarin-loading-dose-guided-by-pharmacogenetics-is-effective-and-safe-in-cardioembolic-stroke-patients-a-randomized-prospective-study
#17
Tereza Ruzickova, Martin Sramek, Vojtech Kaplan, Simona Kumstyrova, Zuzana Lacinova, Petr Jansky, Hana Magerova, Ivana Sarbochova, Jaroslava Paulasova Schwabova, Vaclav Matoska, Ales Tomek
Warfarin treatment is commonly started with a fixed loading dose that might be associated with an increased risk of bleeding. An individual maintenance dose can then be estimated based on a pharmacogenetic algorithm. Starting treatment with the estimated dose implies a longer time to reach the therapeutic range. Our goal was to compare the safety and efficacy of initiating warfarin treatment with a loading dose guided by pharmacogenetics versus a maintenance dose. The primary endpoint was time in the therapeutic range (TTR) in the first 10 days of treatment...
January 16, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30647444/cost-effectiveness-analysis-of-pharmacogenomics-guided-clopidogrel-treatment-in-spanish-patients-undergoing-percutaneous-coronary-intervention
#18
Vasilios Fragoulakis, Marina Bartsakoulia, Xando Díaz-Villamarín, Konstantina Chalikiopoulou, Konstantina Kehagia, Jesús Gabriel Sánchez Ramos, Luis Javier Martínez-González, Maria Gkotsi, Eva Katrali, Efthimios Skoufas, Athanassios Vozikis, Anne John, Bassam R Ali, Sarah Wordsworth, Cristina L Dávila-Fajardo, Theodora Katsila, George P Patrinos, Christina Mitropoulou
Clopidogrel is an antiplatelet drug given to patients before and after having a percutaneous coronary intervention (PCI). Genomic variants in the CYP2C19 gene are associated with variable enzyme activities affecting drug metabolism and hence, patients with reduced or increased enzymatic function have increased risk of bleeding. We conducted a cost-effectiveness analysis to compare a pharmacogenomics versus a non-pharmacogenomics-guided clopidogrel treatment for coronary artery syndrome patients undergoing PCI in the Spanish healthcare setting...
January 16, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30647443/a-single-nucleotide-polymorphism-of-il6-receptor-is-associated-with-response-to-tocilizumab-in-rheumatoid-arthritis-patients
#19
Cécile Luxembourger, Adeline Ruyssen-Witrand, Chayma Ladhari, Cécile Rittore, Yannick Degboe, Jean-Francis Maillefert, Philippe Gaudin, Hubert Marotte, Daniel Wendling, Christian Jorgensen, Alain Cantagrel, Arnaud Constantin, Delphine Nigon, Isabelle Touitou, Jacques-Eric Gottenberg, Yves-Marie Pers
Biological disease-modifying anti-rheumatic drugs (bDMARDs) have changed care of patients with rheumatoid arthritis (RA). However, bDMARDs are costly, can lead to serious infections, and induce a sustained remission in only 30% of RA patients. In this study, we sought to determine if the clinical response to treatment with Tocilizumab (TCZ), an IL-6 inhibitor, varied with genetic background. The efficacy of TCZ was assessed using the European League Against Rheumatism (EULAR) response criteria, measured after 3 months of treatment in two samples of French RA patients (TOCI and ROC studies)...
January 16, 2019: Pharmacogenomics Journal
https://read.qxmd.com/read/30250148/association-between-slco1b1-t521c-polymorphism-and-risk-of-statin-induced-myopathy-a-meta-analysis
#20
Qian Xiang, Shu-Qing Chen, Ling-Yue Ma, Kun Hu, Zhuo Zhang, Guang-Yan Mu, Qiu-Fen Xie, Xiao-Dan Zhang, Yi-Min Cui
Numerous studies have illustrated the relationship between SLCO1B1 T521C polymorphism and statin-induced myopathy risk; however, this association is not consistent. Three electronic databases (PubMed, EMBASE, and the Cochrane Library) were searched from inception to October 2017 to identify potential studies. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated from different genetic models by using a random-effects model. Fourteen studies comprising 3265 myopathy patients and 7743 controls were included...
December 2018: Pharmacogenomics Journal
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