journal
MENU ▼
Read by QxMD icon Read
search

Pharmacogenomics Journal

journal
https://www.readbyqxmd.com/read/29305589/astrocyte-specific-transcriptome-responses-to-chronic-ethanol-consumption
#1
Emma K Erickson, Sean P Farris, Yuri A Blednov, R Dayne Mayfield, R Adron Harris
Astrocytes play critical roles in central nervous system (CNS) homeostasis and are implicated in the pathogenesis of neurological and psychiatric conditions, including drug dependence. Little is known about the effects of chronic ethanol consumption on astrocyte gene expression. To address this gap in knowledge, we performed transcriptome-wide RNA sequencing of astrocytes isolated from the prefrontal cortex (PFC) of mice following chronic ethanol consumption. Differential expression analysis revealed ethanol-induced changes unique to astrocytes that were not identified in total homogenate preparations...
January 5, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29302041/analysis-of-cytokine-immune-response-profile-in-response-to-inflammatory-stimuli-in-mice-with-genetic-defects-in-fetal-and-adult-hemoglobin-chain-expression
#2
Ismat Khatri, Christian Alexander, Klaus Brandenburg, Zhiqi Chen, Adrian Heini, Didier Heumann, Jean-Pierre Mach, Vienna Mazzoli, Ernst Rietschel, Alexey Tersikh, Artur Ulmer, Kai Yu, Ulrich Zähringer, Reginald Gorczynski
Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice. To investigate the role of fetal hemoglobin we derived mice with homzygous deletions for either of the two major βchains, HgbβmaKO or HgbβmiKO. Hgbβmi is the most prominent fetal Hgbβ chain, with Hgbβma more prominent in adult mice. Mice lacking another fetal Hgb chain, HgbεKO, died in utero. CHO cells transfected with cloned Hgb chains were used to produce proteins for preparation of rabbit heteroantibodes...
January 4, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29298996/the-phosphatidylinositide-3-kinase-pi3k-signaling-pathway-is-a-determinant-of-zileuton-response-in-adults-with-asthma
#3
Amber Dahlin, Weiliang Qiu, Augusto A Litonjua, John J Lima, Mayumi Tamari, Michiaki Kubo, Charles G Irvin, Stephen P Peters, Ann C Wu, Scott T Weiss, Kelan G Tantisira
Variable responsiveness to zileuton, a leukotriene antagonist used to treat asthma, may be due in part to genetic variation. While individual SNPs were previously associated with zileuton-related lung function changes, specific quantitative trait loci (QTLs) and biological pathways that may contribute have not been identified. In this study, we investigated the hypothesis that genetic variation within biological pathways is associated with zileuton response. We performed an integrative QTL mapping and pathway enrichment study to investigate data from a GWAS of zileuton response, in addition to mRNA expression profiles and leukotriene production data from lymphoblastoid cell lines (LCLs) (derived from asthmatics) that were treated with zileuton or ethanol (control)...
January 3, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29298995/nuclear-receptor-gene-polymorphisms-and-warfarin-dose-requirements-in-the-quebec-warfarin-cohort
#4
Payman Shahabi, Félix Lamothe, Stéphanie Dumas, Étienne Rouleau-Mailloux, Yassamin Feroz Zada, Sylvie Provost, Geraldine Asselin, Ian Mongrain, Diane Valois, Marie-Josée Gaulin Marion, Louis-Philippe Lemieux Perreault, Sylvie Perreault, Marie-Pierre Dubé
Warfarin is primarily metabolized by cytochrome 2C9, encoded by gene CYP2C9. Here, we investigated whether variants in nuclear receptor genes which regulate the expression of CYP2C9 are associated with warfarin response. We used data from 906 warfarin users from the Quebec Warfarin Cohort (QWC) and tested the association of warfarin dose requirement at 3 months following the initiation of therapy in nine nuclear receptor genes: NR1I3, NR1I2, NR3C1, ESR1, GATA4, RXRA, VDR, CEBPA, and HNF4A. Three correlated SNPs in the VDR gene (rs4760658, rs11168292, and rs11168293) were associated with dose requirements of warfarin (P = 2...
January 3, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29298994/cost-effectiveness-of-hla-dqb1-hla-b-pharmacogenetic-guided-treatment-and-blood-monitoring-in-us-patients-taking-clozapine
#5
François R Girardin, Antoine Poncet, Arnaud Perrier, Nathalie Vernaz, Mark Pletscher, Caroline F Samer, Jeffrey A Lieberman, Jean Villard
Less than 1% of adult patients with schizophrenia taking clozapine develop agranulocytosis, and most of these cases occur within the first weeks of treatment. The human leukocyte antigen (HLA) region has been associated with genetic susceptibility to clozapine-induced agranulocytosis (single amino acid changes in HLA-DQB1 (126Q) and HLA-B (158T)). The current study aimed to evaluate the cost-effectiveness, from a healthcare provider's perspective, of an HLA genotype-guided approach in patients with treatment-resistant schizophrenia who were taking clozapine and to compare the results with the current absolute neutrophil count monitoring (ANCM) schemes used in the USA...
January 3, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29282365/genetic-and-clinic-predictors-of-new-onset-diabetes-mellitus-after-transplantation
#6
Núria Saigi-Morgui, Lina Quteineh, Pierre-Yves Bochud, Severine Crettol, Zoltán Kutalik, Nicolas J Mueller, Isabelle Binet, Christian Van Delden, Jürg Steiger, Paul Mohacsi, Jean-Francois Dufour, Paola M Soccal, Manuel Pascual, Chin B Eap
New Onset Diabetes after Transplantation (NODAT) is a frequent complication after solid organ transplantation, with higher incidence during the first year. Several clinical and genetic factors have been described as risk factors of Type 2 Diabetes (T2DM). Additionally, T2DM shares some genetic factors with NODAT. We investigated if three genetic risk scores (w-GRS) and clinical factors were associated with NODAT and how they predicted NODAT development 1 year after transplantation. In both main (n = 725) and replication (n = 156) samples the clinical risk score was significantly associated with NODAT (ORmain: 1...
December 27, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29282364/mir-pharmacogenetics-of-vincristine-and-peripheral-neurotoxicity-in-childhood-b-cell-acute-lymphoblastic-leukemia
#7
Ángela Gutierrez-Camino, Maitane Umerez, Idoia Martin-Guerrero, Nagore García de Andoin, Borja Santos, Ana Sastre, Aizpea Echebarria-Barona, Itziar Astigarraga, Aurora Navajas, Africa Garcia-Orad
Vincristine (VCR), an important component of childhood acute lymphoblastic leukemia (ALL) therapy, can cause sensory and motor neurotoxicity. This neurotoxicity could lead to dose reduction or treatment discontinuation, which could in turn reduce survival. In this line, several studies associated peripheral neurotoxicity and polymorphisms in genes involved in pharmacokinetics (PK) and pharmacodynamics (PD) of VCR. Nowadays, it is well known that these genes are regulated by microRNAs (miRNAs) and SNPs in miRNAs could modify their levels or function...
December 27, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29282363/the-impact-of-genetic-polymorphisms-on-cyp1a2-activity-in-humans-a-systematic-review-and-meta-analysis
#8
Nut Koonrungsesomboon, Rapheephorn Khatsri, Penwisa Wongchompoo, Supanimit Teekachunhatean
A large interindividual variation in the activity of cytochrome P450 1A2 (CYP1A2) raises concern about therapeutic failure or toxicity when medical professionals prescribe drugs extensively metabolized by CYP1A2. To date, a number of studies have assessed the association between genetic polymorphisms and CYP1A2 activity; however, there are controversies as to the functional importance of CYP1A2 polymorphisms on the metabolism of CYP1A2 substrates. This systematic review and meta-analysis assessed the effects of genetic polymorphisms on CYP1A2 activity, as measured by caffeine metabolism, in a total of 3570 individual subjects...
December 27, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29282362/genetic-variants-in-the-vegf-pathway-as-prognostic-factors-in-stages-ii-and-iii-colon-cancer
#9
Pau Riera, Anna C Virgili, Juliana Salazar, Ana Sebio, María Tobeña, Ivana Sullivan, David Páez
The role of vascular endothelial growth factor (VEGF) gene polymorphisms in the prognosis of colon cancer prognosis remains unclear. We evaluated the influence of 28 single-nucleotide polymorphisms in 12 genes in the VEGF pathway on the prognosis of 347 patients with stage II-III colon cancer. We found that rs9513070 (VEGFR1) and rs1137282 (KRAS) were associated with overall survival in stage II colon cancer patients (p = 0.025 and p = 0.001, respectively). When primary tumor location was considered, rs9513070 was also associated with relapse-free and overall survival (p = 0...
December 27, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29282361/influence-of-bcl2l11-polymorphism-on-osteonecrosis-during-treatment-of-childhood-acute-lymphoblastic-leukemia
#10
Maria Plesa, Vincent Gagné, Sanja Glisovic, Melissa Younan, Bahram Sharif-Askari, Caroline Laverdière, Nathalie Alos, Jean-Marie Leclerc, Stephen E Sallan, Donna Neuberg, Jeffery L Kutok, Lewis B Silverman, Daniel Sinnett, Maja Krajinovic
Osteonecrosis (ON) is corticosteroid-related complication, reported in children with acute lymphoblastic leukemia (ALL). We have previously found that polymorphisms in BCL2L11 gene coding for pro-apoptotic Bim protein influence reduction of overall survival (OS) in a corticosteroid (CS) dose-dependent manner in childhood ALL patients. The same set of SNPs was here investigated for an association with CS-related ON assessed retrospectively in 304 children with ALL from Quebec (QcALL cohort) who received Dana-Farber Cancer Institute (DFCI) ALL treatment protocols...
December 27, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29273767/the-rs2108622-polymorphism-is-related-to-the-early-risk-of-ischemic-stroke-in-non-valvular-atrial-fibrillation-subjects-under-oral-anticoagulation
#11
L Colàs-Campàs, J L Royo, M V Montserrat, C Marzo, J Molina-Seguín, I Benabdelhak, S Cambray, F Purroy
Oral anticoagulant treatments, such as vitamin K antagonists (VKAs), are the main treatments administered to atrial fibrillation (AF) patients in order to prevent ischemic stroke (IS). However, the genes involved in the VKA metabolism can undergo variations in a single nucleotide (SNP). These SNPs may then affect the VKA target enzyme (VKORC1), VKA degradation enzyme (CYP2C9), and vitamin K bioavailability enzyme (CYP4F2). We genotyped these SNPs in a cohort of patients with non-valvular AF who were under VKA treatment after suffering an IS...
December 22, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29205207/therapeutic-targeting-of-membrane-associated-grp78-in-leukemia-and-lymphoma-preclinical-efficacy-in-vitro-and-formal-toxicity-study-of-bmtp-78-in-rodents-and-primates
#12
D I Staquicini, S D'Angelo, F Ferrara, K Karjalainen, G Sharma, T L Smith, C A Tarleton, D E Jaalouk, A Kuniyasu, W B Baze, B K Chaffee, P W Hanley, K F Barnhart, E Koivunen, S Marchiò, R L Sidman, J E Cortes, H M Kantarjian, W Arap, R Pasqualini
Translation of drug candidates into clinical settings requires demonstration of preclinical efficacy and formal toxicology analysis for filling an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA). Here, we investigate the membrane-associated glucose response protein 78 (GRP78) as a therapeutic target in leukemia and lymphoma. We evaluated the efficacy of the GRP78-targeted proapoptotic drug bone metastasis targeting peptidomimetic 78 (BMTP-78), a member of the D(KLAKLAK)2-containing class of agents...
December 5, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29205206/applications-of-pharmacogenomics-in-regulatory-science-a-product-life-cycle-review
#13
W C Tan-Koi, P C Leow, Y Y Teo
With rapid developments of pharmacogenomics (PGx) and regulatory science, it is important to understand the current PGx integration in product life cycle, impact on clinical practice thus far and opportunities ahead. We conducted a cross-sectional review on PGx-related regulatory documents and implementation guidelines in the United States and Europe. Our review found that although PGx-related guidance in both markets span across the entire product life cycle, the scope of implementation guidelines varies across two continents...
December 5, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29205205/gene-expression-and-linkage-analysis-implicate-cblb-as-a-mediator-of-rituximab-resistance
#14
J Jack, G W Small, C C Brown, T M Havener, H L McLeod, A A Motsinger-Reif, K L Richards
Elucidating resistance mechanisms for therapeutic monoclonal antibodies (MAbs) is challenging, because they are difficult to study in non-human models. We therefore developed a strategy to genetically map in vitro drug sensitivity, identifying genes that alter responsiveness to rituximab, a therapeutic anti-CD20 MAb that provides significant benefit to patients with B-cell malignancies. We discovered novel loci with genome-wide mapping analyses and functionally validated one of these genes, CBLB, which causes rituximab resistance when knocked down in lymphoma cells...
December 5, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29205204/mthfr-ts-and-xrcc1-genetic-variants-may-affect-survival-in-patients-with-myelodysplastic-syndromes-treated-with-supportive-care-or-azacitidine
#15
G Visani, F Loscocco, A Ruzzo, S Galimberti, F Graziano, M T Voso, E Giacomini, C Finelli, E Ciabatti, E Fabiani, S Barulli, A Volpe, D Magro, P Piccaluga, F Fuligni, M Vignetti, P Fazi, A Piciocchi, E Gabucci, M Rocchi, M Magnani, A Isidori
We evaluated the impact of genomic polymorphisms in folate-metabolizing, DNA synthesis and DNA repair enzymes on the clinical outcome of 108 patients with myelodysplastic syndromes (MDS) receiving best supportive care (BSC) or azacitidine. A statistically significant association between methylenetetrahydrofolate reductase (MTHFR) 677T/T, thymidylate synthase (TS) 5'-untranslated region (UTR) 3RG, TS 3'-UTR -6 bp/-6 bp, XRCC1 399G/G genotypes and short survival was found in patients receiving BSC by multivariate analysis (P<0...
December 5, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29160303/the-pnpla3-i148m-variant-is-associated-with-transaminase-elevations-in-type-2-diabetes-patients-treated-with-basal-insulin-peglispro
#16
S Pillai, S Duvvuru, P Bhatnagar, W Foster, M Farmen, S Shankar, C Harris, E Bastyr, B Hoogwerf, A Haupt
Basal insulin peglispro (BIL) is a novel insulin with hepato-preferential action. In phase 3 trials, BIL showed significantly improved glycemic control but higher levels of transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), triglycerides (TGs) and liver fat content (LFC) compared with insulin glargine (GL). As variants in PNPLA3 (I148M) and TM6SF2 (E167K) are associated with nonalcoholic fatty liver disease, we assessed these variants in type 2 diabetes (T2D) patients randomized to receive BIL (n=1822) or GL (n=1270) in three phase 3 trials...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29160302/role-of-cyp24a1-vdr-and-gc-gene-polymorphisms-on-deferasirox-pharmacokinetics-and-clinical-outcomes
#17
S Allegra, J Cusato, S De Francia, A Arduino, F Longo, E Pirro, D Massano, A De Nicolò, A Piga, A D'Avolio
β-Thalassemia patients develop deficiency in vitamin D absorption and liver hydroxylation, resulting in extremely low calcitriol levels. We explored the role of single-nucleotide polymorphisms (SNPs) involved in vitamin D metabolism, transport and activity on deferasirox pharmacokinetics and outcomes (effectiveness trough levels (Ctrough) and the area under the curve (AUC) cutoffs of 20 μg ml(-1) and 360 μg ml(-1) h(-1), respectively; nonresponse AUC limit of 250 μg ml(-1) h(-1)). Ninety-nine β-thalassemic patients were enrolled...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29160301/new-insights-into-the-pharmacogenomics-of-antidepressant-response-from-the-gendep-and-star-d-studies-rare-variant-analysis-and-high-density-imputation
#18
C Fabbri, K E Tansey, R H Perlis, J Hauser, N Henigsberg, W Maier, O Mors, A Placentino, M Rietschel, D Souery, G Breen, C Curtis, L Sang-Hyuk, S Newhouse, H Patel, M Guipponi, N Perroud, G Bondolfi, M O'Donovan, G Lewis, J M Biernacka, R M Weinshilboum, A Farmer, K J Aitchison, I Craig, P McGuffin, R Uher, C M Lewis
Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (SNP), gene and pathway levels. Coverage of genetic variants was increased compared with previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29160300/genome-wide-association-study-identifies-the-common-variants-in-cyp3a4-and-cyp3a5-responsible-for-variation-in-tacrolimus-trough-concentration-in-caucasian-kidney-transplant-recipients
#19
W S Oetting, B Wu, D P Schladt, W Guan, R P Remmel, R B Mannon, A J Matas, A K Israni, P A Jacobson
The immunosuppressant tacrolimus (TAC) is metabolized by both cytochrome P450 3A4 (CYP3A4) and CYP3A5 enzymes. It is common for European Americans (EA) to carry two CYP3A5 loss-of-function (LoF) variants that profoundly reduces TAC metabolism. Despite having two LoF alleles, there is still considerable variability in TAC troughs and identifying additional variants in genes outside of the CYP3A5 gene could provide insight into this variability. We analyzed TAC trough concentrations in 1345 adult EA recipients with two CYP3A5 LoF alleles in a genome-wide association study...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29053139/chronic-fluoxetine-upregulates-activity-protein-and-mrna-levels-of-cytosolic-phospholipase-a2-in-rat-frontal-cortex
#20
J S Rao, R N Ertley, H-J Lee, S I Rapoport, R P Bazinet
This corrects the article DOI: 10.1038/sj.tpj.6500391.
October 17, 2017: Pharmacogenomics Journal
journal
journal
38189
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"