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Pharmacogenomics Journal

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https://www.readbyqxmd.com/read/28094348/weight-of-abcb1-and-por-genes-on-oral-tacrolimus-exposure-in-cyp3a5-nonexpressor-pediatric-patients-with-stable-kidney-transplant
#1
G N Almeida-Paulo, I Dapía García, R Lubomirov, A M Borobia, N L Alonso-Sánchez, L Espinosa, A J Carcas-Sansuán
Tacrolimus (TAC) is highly effective for the prevention of acute organ rejection. However, its clinical use may be challenging due to its large interindividual pharmacokinetic variability, which can be partially explained by genetic variations in TAC-metabolizing enzymes and transporters. The aim of this study was to evaluate the influence of genetic and clinical factors on TAC pharmacokinetic variability in 21 stable pediatric renal transplant patients. This study was nested in a previous Prograf to Advagraf conversion clinical trial...
January 17, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28045129/the-glutathione-transferase-mu-null-genotype-leads-to-lower-6-mmpr-levels-in-patients-treated-with-azathioprine-but-not-with-mercaptopurine
#2
M M T J Broekman, D R Wong, G J A Wanten, H M Roelofs, C J van Marrewijk, O H Klungel, A L M Verbeek, P M Hooymans, H-J Guchelaar, H Scheffer, L J J Derijks, M J H Coenen, D J de Jong
The conversion of azathioprine (AZA) to mercaptopurine (MP) is mediated by glutathione transferase Mu1 (GSTM1), alpha1 (GSTA1) and alpha2 (GSTA2). We designed a case-control study with data from the TOPIC trial to explore the effects of genetic variation on steady state 6-methylmercaptopurine ribonucleotide (6-MMPR) and 6-thioguanine nucleotide (6-TGN) metabolite levels. We included 199 patients with inflammatory bowel disease (126 on AZA and 73 on MP). GSTM1-null genotype carriers on AZA had two-fold lower 6-MMPR levels than AZA users carrying one or two copies of GSTM1 (2239 (1006-4587) versus 4371 (1897-7369) pmol/8 × 10(8) RBCs; P<0...
January 3, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28045128/epigenomics-alternations-and-dynamic-transcriptional-changes-in-responses-to-5-fluorouracil-stimulation-reveal-mechanisms-of-acquired-drug-resistance-of-colorectal-cancer-cells
#3
Y Shen, M Tong, Q Liang, Y Guo, H Q Sun, W Zheng, L Ao, Z Guo, F She
A drug-induced resistant cancer cell is different from its parent cell in transcriptional response to drug treatment. The distinct transcriptional response pattern of a drug-induced resistant cancer cell to drug treatment might be introduced by acquired DNA methylation aberration in the cell exposing to sustained drug stimulation. In this study, we performed both transcriptional and DNA methylation profiles of the HCT-8 wild-type cells (HCT-8/WT) for human colorectal cancer (CRC) and the 5-fluorouracil (5-FU)-induced resistant cells (HCT-8/5-FU) after treatment with 5-FU for 0, 24 and 48 h...
January 3, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27995989/pharmacogenetic-variants-associated-with-outcome-in-patients-with-advanced-gastric-cancer-treated-with-fluoropyrimidine-and-platinum-based-triplet-combinations-a-pooled-analysis-of-three-prospective-studies
#4
D Meulendijks, E A Rozeman, A Cats, K Sikorska, M Joerger, M J Deenen, J H Beijnen, J H M Schellens
The main treatment for advanced gastric cancer is fluoropyrimidine and platinum-based chemotherapy. We investigated the clinical validitiy of 19 candidate pharmacogenetic variants in ENOSF1 (enolase superfamily member 1), TYMS, CDA, MTHFR, TYMP, DPYD, ERCC1, ERCC2, GSTP1, GSTT1, GSTM1, CYP3A4 and CYP3A5 in relation to overall survival (OS), progression-free survival, objective response rate (ORR) and toxicity in 185 patients receiving triplet chemotherapy. The formal significance threshold was P<0.0026. TYMS VNTR (variable number of 28-bp tandem repeats) 3 R/3 R genotype was formally associated with inferior ORR (odds ratio (OR) 0...
December 20, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27958382/polymorphisms-of-abcc5-and-nos3-genes-influence-doxorubicin-cardiotoxicity-in-survivors-of-childhood-acute-lymphoblastic-leukemia
#5
M Krajinovic, J Elbared, S Drouin, L Bertout, A Rezgui, M Ansari, M-J Raboisson, S E Lipshultz, L B Silverman, S E Sallan, D S Neuberg, J L Kutok, C Laverdière, D Sinnett, G Andelfinger
No abstract text is available yet for this article.
December 13, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27958381/a-polymorphism-in-the-oprm1-3-untranslated-region-is-associated-with-methadone-efficacy-in-treating-opioid-dependence
#6
R C Crist, G A Doyle, E C Nelson, L Degenhardt, N G Martin, G W Montgomery, A J Saxon, W Ling, W H Berrettini
The μ-opioid receptor (MOR) is the primary target of methadone and buprenorphine. The primary neuronal transcript of the OPRM1 gene, MOR-1, contains a ~13 kb 3' untranslated region with five common haplotypes in European-Americans. We analyzed the effects of these haplotypes on the percentage of opioid positive urine tests in European-Americans (n=582) during a 24-week, randomized, open-label trial of methadone or buprenorphine/naloxone (Suboxone) for the treatment of opioid dependence. A single haplotype, tagged by rs10485058, was significantly associated with patient urinalysis data in the methadone treatment group...
December 13, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27958380/influence-of-il6r-gene-polymorphisms-in-the-effectiveness-to-treatment-with-tocilizumab-in-rheumatoid-arthritis
#7
M Maldonado-Montoro, M Cañadas-Garre, A González-Utrilla, M Ángel Calleja-Hernández
In the present study, we aimed to investigate the influence of clinical parameters and single-nucleotide polymorphisms of interleukin-6 receptor (rs12083537, rs2228145, rs4329505 and rs11265618) on response to tocilizumab, TCZ (European League Against Rheumatism (EULAR) response, remission, low disease activity (LDA) and improvement of DAS28). We performed a retrospective cohort study in patients with Rheumatoid Arthritis (RA) treated with TCZ for 12 months. Multivariable analysis showed that the only variable independently associated to satisfactory EULAR response (odds ratio (OR): 0...
December 13, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27958379/a-systems-biology-approach-to-investigate-the-mechanism-of-action-of-trabectedin-in-a-model-of-myelomonocytic-leukemia
#8
L Mannarino, L Paracchini, I Craparotta, M Romano, S Marchini, R Gatta, E Erba, L Clivio, C Romualdi, M D'Incalci, L Beltrame, L Pattini
This study was designed to investigate the mode of action of trabectedin in myelomonocytic leukemia cells by applying systems biology approaches to mine gene expression profiling data and pharmacological assessment of the cellular effects. Significant enrichment was found in regulons of target genes inferred for specific transcription factors, among which MAFB was the most upregulated after treatment and was central in the transcriptional network likely to be relevant for the specific therapeutic effects of trabectedin against myelomonocytic cells...
December 13, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27958378/large-scale-pharmacogenomic-study-of-sulfonylureas-and-the-qt-jt-and-qrs-intervals-charge-pharmacogenomics-working-group
#9
J S Floyd, C M Sitlani, C L Avery, R Noordam, X Li, A V Smith, S M Gogarten, J Li, L Broer, D S Evans, S Trompet, J A Brody, J D Stewart, J D Eicher, A A Seyerle, J Roach, L A Lange, H J Lin, J A Kors, T B Harris, R Li-Gao, N Sattar, S R Cummings, K L Wiggins, M D Napier, T Stürmer, J C Bis, K F Kerr, A G Uitterlinden, K D Taylor, D J Stott, R de Mutsert, L J Launer, E L Busch, R Méndez-Giráldez, N Sotoodehnia, E Z Soliman, Y Li, Q Duan, F R Rosendaal, P E Slagboom, K C Wilhelmsen, A P Reiner, Y-DI Chen, S R Heckbert, R C Kaplan, K M Rice, J W Jukema, A D Johnson, Y Liu, D O Mook-Kanamori, V Gudnason, J G Wilson, J I Rotter, C C Laurie, B M Psaty, E A Whitsel, L A Cupples, B H Stricker
Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals...
December 13, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27958377/a-pharmacogenomic-study-on-the-pharmacokinetics-of-tacrolimus-in-healthy-subjects-using-the-dmettm-plus-platform
#10
Y Choi, F Jiang, H An, H J Park, J H Choi, H Lee
No abstract text is available yet for this article.
December 13, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27897269/an-integrated-pharmacokinetic-pharmacogenomic-analysis-of-abcb1-and-slco1b1-polymorphisms-on-edoxaban-exposure
#11
A G Vandell, J Lee, M Shi, I Rubets, K S Brown, J R Walker
Edoxaban and its low-abundance, active metabolite M4 are substrates of P-glycoprotein (P-gp; MDR1) and organic anion transporter protein 1B1 (OATP1B1), respectively, and pharmacological inhibitors of P-gp and OATP1B1 can affect edoxaban and M4 pharmacokinetics (PK). In this integrated pharmacogenomic analysis, genotype and concentration-time data from 458 healthy volunteers in 14 completed phase 1 studies were pooled to examine the impact on edoxaban PK parameters of allelic variants of ABCB1 (rs1045642: C3435T) and SLCO1B1 (rs4149056: T521C), which encode for P-gp and OATP1B1...
November 29, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27897268/germline-polymorphisms-as-biomarkers-of-tumor-response-in-colorectal-cancer-patients-treated-with-anti-egfr-monoclonal-antibodies-a-systematic-review-and-meta-analysis
#12
E K Morgen, H-J Lenz, D J Jonker, D Tu, G Milano, F Graziano, J Zalcberg, C S Karapetis, A Dobrovic, C J O'Callaghan, G Liu
Studies of germline polymorphisms as predictors of tumor response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody agents in metastatic colorectal cancer have reported inconsistent results. We performed a systematic review of studies from 1990 to September 2015, followed by random-effects meta-analyses for polymorphisms examined in at least three studies. Of 87 studies, 40 passed the criteria for systematic review and 23 for meta-analysis. The polymorphisms suitable for meta-analysis were CCND1 (rs17852153), COX2 (rs20417), EGF (rs4444903), EGFR (rs712829, rs11543848, 3'UTR CA repeat), FCGR2A (rs1801274), FCGR3A (rs396991), IL8 (rs4073), KRAS (rs61764370) and VEGFA (rs3025039)...
November 29, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27897267/increasing-bmi-is-associated-with-reduced-expression-of-p-glycoprotein-abcb1-gene-in-the-human-brain-with-a-stronger-association-in-african-americans-than-caucasians
#13
J Vendelbo, R H Olesen, J K Lauridsen, J Rungby, J E Kleinman, T M Hyde, A Larsen
The efflux pump, p-glycoprotein, controls bioavailability and excretion of pharmaceutical compounds. In the blood-brain barrier, p-glycoprotein regulates the delivery of pharmaceutical substances to the brain, influencing efficacy and side effects for some drugs notably antipsychotics. Common side effects to antipsychotics include obesity and metabolic disease. Polymorphisms in the ABCB1 gene coding for p-glycoprotein are associated with more severe side effects to neuro-pharmaceuticals as well as weight gain, indicating a potential link between p-glycoprotein function and metabolic regulation...
November 29, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27845419/abc-transporter-polymorphisms-are-associated-with-irinotecan-pharmacokinetics-and-neutropenia
#14
M Li, E L Seiser, R M Baldwin, J Ramirez, M J Ratain, F Innocenti, D L Kroetz
Neutropenia is a common dose-limiting toxicity associated with irinotecan treatment. Although UGT1A1 variants have been associated with neutropenia, a fraction of neutropenia risk remains unaccounted for. To identify additional genetic markers contributing to variability in irinotecan pharmacokinetics and neutropenia, a regression analysis was performed in 78 irinotecan-treated patients to analyze comprehensively three hepatic efflux transporter genes (ABCB1, ABCC1 and ABCG2). rs6498588 (ABCC1) and rs12720066 (ABCB1) were associated with increased SN-38 exposure, and rs17501331 (ABCC1) and rs12720066 were associated with lower absolute neutrophil count nadir...
November 15, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27779249/the-global-spectrum-of-protein-coding-pharmacogenomic-diversity
#15
G E B Wright, B Carleton, M R Hayden, C J D Ross
Differences in response to medications have a strong genetic component. By leveraging publically available data, the spectrum of such genomic variation can be investigated extensively. Pharmacogenomic variation was extracted from the 1000 Genomes Project Phase 3 data (2504 individuals, 26 global populations). A total of 12 084 genetic variants were found in 120 pharmacogenes, with the majority (90.0%) classified as rare variants (global minor allele frequency <0.5%), with 52.9% being singletons. Common variation clustered individuals into continental super-populations and 23 pharmacogenes contained highly differentiated variants (FST>0...
October 25, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27779248/association-of-cth-variant-with-sinusoidal-obstruction-syndrome-in-children-receiving-intravenous-busulfan-and-cyclophosphamide-before-hematopoietic-stem-cell-transplantation
#16
P Huezo-Diaz Curtis, C R S Uppugunduri, J Muthukumaran, M A Rezgui, C Peters, P Bader, M Duval, H Bittencourt, Maja Krajinovic, Marc Ansari
Sinusoidal obstruction syndrome (SOS) is a severe complication of hematopoietic stem cell transplantation (HSCT) that can be fatal, often attributed to the conditioning regimen prior to HSCT. We evaluated the association of SOS risk with gene variants in cystathionase (CTH), an enzyme involved in glutathione synthesis, in 76 children receiving intravenous busulfan (Bu) before HSCT. Our results indicated an association with CTHc.1364 G>T (ORTT=10.6, 95% confidence interval (CI)=2.16, 51.54) and SOS risk, which was sex dependent (female patients, ORTT=21...
October 25, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27779247/hla-b18-as-risk-factor-of-liver-fibrosis-progression-in-hiv-hcv-treatment-experienced-patients
#17
M Frías, D Rodríguez-Cano, F Cuenca-López, J Macías, A Gordon, B Manzanares-Martín, J A Pineda, Á Camacho, J Torre-Cisneros, J Peña, A Rivero-Juárez, A Rivero
No abstract text is available yet for this article.
October 25, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27779246/are-patients-willing-to-incur-out-of-pocket-costs-for-pharmacogenomic-testing
#18
S J Bielinski, J L St Sauver, J E Olson, M L Wieland, C R Vitek, E J Bell, M E Mc Gree, D J Jacobson, J B McCormick, P Y Takahashi, J L Black, P J Caraballo, R R Sharp, T J Beebe, R M Weinshilboum, L Wang, V L Roger
No abstract text is available yet for this article.
October 25, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27779245/association-between-drd2-and-drd3-gene-polymorphisms-and-gastrointestinal-symptoms-induced-by-levodopa-therapy-in-parkinson-s-disease
#19
M Rieck, A F Schumacher-Schuh, V Altmann, S M Callegari-Jacques, C R M Rieder, M H Hutz
Levodopa is the most used drug to treat motor symptoms in Parkinson's disease (PD). However, dopaminergic side effects such as nausea and vomiting may occur. Several evidences indicate a major role for dopamine receptors D2 (DRD2) and D3 (DRD3) in emetic activity. The aim of this study was to investigate the relationship of DRD2 rs1799732 and DRD3 rs6280 gene polymorphisms with gastrointestinal (GI) symptoms induced by levodopa in PD patients. Two hundred and seventeen PD patients on levodopa therapy were investigated...
October 25, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27779244/predictive-value-of-atp7b-brca1-brca2-parp1-uimc1-rap80-hoxa9-daxx-txn-trx1-thbs1-tsp1-and-prr13-txr1-genes-in-patients-with-epithelial-ovarian-cancer-who-received-platinum-taxane-first-line-therapy
#20
S Pontikakis, C Papadaki, M Tzardi, M Trypaki, M Sfakianaki, F Koinis, E Lagoudaki, L Giannikaki, A Kalykaki, E Kontopodis, Z Saridaki, N Malamos, V Georgoulias, J Souglakos
To evaluate the predictive value of genes involved in resistance to platinum-taxane chemotherapy in patients with epithelial ovarian cancer (EOC). Microdissected formalin-fixed tumoral samples from 187 EOC patients' primary tumors (90 and 97 samples from matched patients in the experimental and validation sets, respectively) were analyzed. All specimens were analyzed for ATP7b, BRCA1, BRCA2, PARP1, UIMC1(RAP80), HOXA9, DAXX, TXN (TRX1), THBS1 (TSP1) and PRR13 (TXR1) mRNA expression by quantitative real-time PCR...
October 25, 2016: Pharmacogenomics Journal
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