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Pharmacogenomic

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https://www.readbyqxmd.com/read/28730340/cyp2d6-genotype-is-not-associated-with-survival-in-breast-cancer-patients-treated-with-tamoxifen-results-from-a-population-based-study
#1
D L Hertz, K M Kidwell, S G Hilsenbeck, S Oesterreich, C K Osborne, S Philips, C Chenault, R J Hartmaier, T C Skaar, M J Sikora, J M Rae
PURPOSE: A number of studies have tested the hypothesis that breast cancer patients with low-activity CYP2D6 genotypes achieve inferior benefit from tamoxifen treatment, putatively due to lack of metabolic activation to endoxifen. Studies have provided conflicting data, and meta-analyses suggest a small but significant increase in cancer recurrence, necessitating additional studies to allow for accurate effect assessment. We conducted a retrospective pharmacogenomic analysis of a prospectively collected community-based cohort of patients with estrogen receptor-positive breast cancer to test for associations between low-activity CYP2D6 genotype and disease outcome in 500 patients treated with adjuvant tamoxifen monotherapy and 500 who did not receive any systemic adjuvant therapy...
July 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28729456/mechanistic-multi-tissue-modeling-of-gilz-regulation-integrating-circadian-gene-expression-with-receptor-mediated-corticosteroid-pharmacodynamics
#2
Vivaswath S Ayyar, Debra C DuBois, Richard R Almon, William J Jusko
The glucocorticoid-induced leucine zipper (GILZ) is an important mediator of anti-inflammatory corticosteroid action. The pharmacokinetic/pharmacodynamic/pharmacogenomic effects of acute and chronic methylprednisolone (MPL) dosing on the tissue-specific dynamics of GILZ expression were examined in rats. A mechanism-based model was developed to investigate and integrate the role of MPL and circadian rhythms on the transcriptional enhancement of GILZ in multiple tissues. Animals received a single 50 mg/kg intramuscular bolus or a seven-day 0...
July 20, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28723497/pharmacogenomic-markers-of-targeted-therapy-toxicity-in-patients-with-metastatic-renal-cell-carcinoma
#3
Guillermo de Velasco, Kathryn P Gray, Lana Hamieh, Yuksel Urun, Hallie A Carol, Andre P Fay, Sabina Signoretti, David J Kwiatkowski, David F McDermott, Matthew Freedman, Mark M Pomerantz, Toni K Choueiri
BACKGROUND: Targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) may be associated with a high rate of toxicity that undermines treatment efficacy and patient quality of life. Polymorphisms in genes involved in the pharmacokinetic pathways of TTs may predict toxicity. OBJECTIVE: To investigate whether selected single-nucleotide polymorphisms (SNPs) in three core genes involved in the metabolism and transport of sunitinib and the mTOR inhibitors everolimus and temsirolimus are associated with adverse events (AEs)...
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28722800/role-of-the-long-non-coding-rna-gas5-in-glucocorticoid-response-in-children-with-inflammatory-bowel-disease
#4
Marianna Lucafò, Alessia Di Silvestre, Maurizio Romano, Alice Avian, Roberta Antonelli, Stefano Martelossi, Samuele Naviglio, Alberto Tommasini, Gabriele Stocco, Alessandro Ventura, M D Giuliana Decorti, Sara De Iudicibus
Glucocorticoids (GCs) are widely employed in inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first-line treatment for inducing remission in inflammatory bowel disease (IBD). Given the high incidence of suboptimal response, associated with a significant number of side effects, that are particularly severe in paediatric patients, the identification of subjects that are most likely to respond poorly to GCs is extremely important. Recent evidence suggests that the long non-coding RNA (lncRNA) GAS5 could be a potential marker of GC resistance...
July 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28719598/the-predictive-value-of-abcb1-abcg2-cyp3a4-5-and-cyp2d6-polymorphisms-for-risperidone-and-aripiprazole-plasma-concentrations-and-the-occurrence-of-adverse-drug-reactions
#5
C Rafaniello, M Sessa, F F Bernardi, M Pozzi, S Cheli, D Cattaneo, S Baldelli, M Molteni, R Bernardini, F Rossi, E Clementi, C Bravaccio, S Radice, A Capuano
We investigated in ninety Caucasian pediatric patients the impact of the main polymorphisms occurring in CYP3A, CYP2D6, ABCB1 and ABCG2 genes on second-generation antipsychotics plasma concentrations, and their association with the occurrence of adverse drug reactions. Patients with the CA/AA ABCG2 genotype had a statistically significant lower risperidone plasma concentration/dose ratio (Ct/ds) (P-value: 0.007) and an higher estimated marginal probability of developing metabolism and nutrition disorders as compared to the ABCG2 c...
July 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28719597/pharmacogenomics-study-of-thiazide-diuretics-and-qt-interval-in-multi-ethnic-populations-the-cohorts-for-heart-and-aging-research-in-genomic-epidemiology
#6
A A Seyerle, C M Sitlani, R Noordam, S M Gogarten, J Li, X Li, D S Evans, F Sun, M A Laaksonen, A Isaacs, K Kristiansson, H M Highland, J D Stewart, T B Harris, S Trompet, J C Bis, G M Peloso, J A Brody, L Broer, E L Busch, Q Duan, A M Stilp, C J O'Donnell, P W Macfarlane, J S Floyd, J A Kors, H J Lin, R Li-Gao, T Sofer, R Méndez-Giráldez, S R Cummings, S R Heckbert, A Hofman, I Ford, Y Li, L J Launer, K Porthan, C Newton-Cheh, M D Napier, K F Kerr, A P Reiner, K M Rice, J Roach, B M Buckley, E Z Soliman, R de Mutsert, N Sotoodehnia, A G Uitterlinden, K E North, C R Lee, V Gudnason, T Stürmer, F R Rosendaal, K D Taylor, K L Wiggins, J G Wilson, Y-DI Chen, R C Kaplan, K Wilhelmsen, L A Cupples, V Salomaa, C van Duijn, J W Jukema, Y Liu, D O Mook-Kanamori, L A Lange, R S Vasan, A V Smith, B H Stricker, C C Laurie, J I Rotter, E A Whitsel, B M Psaty, C L Avery
Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment...
July 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28719596/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
#7
T Magnes, T Melchardt, C Hufnagl, L Weiss, C Mittermair, D Neureiter, E Klieser, G Rinnerthaler, S Roesch, A Gaggl, R Greil, A Egle
FCGR2A-H131R and FCGR3A-V157F are single-nucleotide polymorphisms known to influence the outcome of patients treated with rituximab, cetuximab and trastuzumab. We investigated the impact of these polymorphisms on the clinical outcome of 103 patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with a platinum compound, fluorouracil and cetuximab as palliative first-line therapy. The survival of patients with FCGR2A-131H/H and/or FCGR3A-157V/V genotypes was significantly longer compared with patients carrying 131R and 157F alleles (median progression-free survival (PFS): 5...
July 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28718665/prevalence-of-low-vitamin-d-in-patients-with-breast-cancer-in-a-predominantly-hispanic-population-at-the-american-mexican-border
#8
Safa E Farrag, Alok K Dwivedi, Salman Otoukesh, Nabeel J Badri, Luis A Sanchez, Zeina A Nahleh
INTRODUCTION: Low level of vitamin D (VD) has been linked with a higher risk of cancers. The aim of this study was to assess the prevalence of low VD in patients with breast cancer in a predominantly Mexican Hispanic/Latino patient population, a fast growing and relatively understudied population. MATERIALS/METHODS: We sought to evaluate the serum VD levels in breast cancer patients diagnosed at the Texas Tech University Breast Cancer Center in El Paso, TX, between May 2013 and May2014 via a retrospective chart review of the Electronic Medical Records...
July 18, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28717926/clinical-evaluation-of-modified-release-and-immediate-release-tacrolimus-formulations
#9
Simon Tremblay, Rita R Alloway
The science of drug delivery has evolved considerably and has led to the development of multiple sustained release formulations. Each of these formulations can present particular challenges in terms of clinical evaluation and necessitate careful study to identify their optimal use in practice. Tacrolimus is an immunosuppressive agent that is widely used in organ transplant recipients. However, it is poorly soluble, has an unpredictable pharmacokinetic profile subject to important genetic polymorphisms and drug-drug interactions, and has a narrow therapeutic index...
July 17, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28711144/genetics-of-juvenile-idiopathic-arthritis
#10
REVIEW
Aimee O Hersh, Sampath Prahalad
Juvenile idiopathic arthritis (JIA) affects approximately 1 in 1000 US children. The cause of JIA is most likely multifactorial and due to an interplay of genetics and environmental factors. This article summarizes the known genetic risk factors for JIA that have been identified, and in some cases replicated, using a variety of methods, including genomewide association and candidate gene association studies. A brief discussion regarding pharmacogenomics and studies to data linking genetics to treatment response and outcomes is included...
August 2017: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/28708103/pharmacogenomics-of-targeted-agents-for-personalization-of-colorectal-cancer-treatment
#11
REVIEW
Alessia Bignucolo, Elena De Mattia, Erika Cecchin, Rossana Roncato, Giuseppe Toffoli
The use of targeted agents in the treatment of metastatic colorectal cancer (CRC) has improved patient outcomes. Anti-epidermal growth factor receptor (anti-EGFR) agents (cetuximab and panitumumab) and antiangiogenic molecules (bevacizumab, regorafeninb, ramucirumab, and aflibercept) have been successfully integrated into clinical practice. Other drugs have been designed to target additional deregulated pathways in CRC, such as MAPK (mitogen-activated protein kinase)/PI3K-AKT (phosphatidylinositol-3-kinase-AKT serine/threonine kinase)/mTOR (mammalian target of rapamycin), HER-2 and 3 ( human epidermal growth factor receptor-2 and -3), and BRAF...
July 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28704821/application-of-the-drugevar-database-in-cancer-genomics-and-pharmacogenomics
#12
Konstantinos Sarris, Angeliki Komianou, George P Patrinos, Theodora Katsila
In the post-genomic era, there is an increasing and urgent need for managing and visualizing big data. Data complexity and size will turn information growth into knowledge growth only if presented in a comprehensive and user-friendly way. In such a context, the information technology community collaborates in a multidisciplinary manner with other scientific fields searching for and/or developing tools and services for data management and visualization. We have previously developed DruGeVar, a comprehensive database that triangulates drugs with genes and pharmacogenomic biomarkers to serve clinical pharmacogenomics...
July 14, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28699700/pharmacogenomics-implementation-considerations-for-selecting-a-reference-laboratory
#13
Teresa T Vo, Gillian C Bell, Aniwaa Owusu Obeng, J Kevin Hicks, Henry M Dunnenberger
One of the initial steps for implementing pharmacogenomics into routine patient care is selecting an appropriate clinical laboratory to perform the testing. With the rapid advances in genotyping technologies, many clinical laboratories are now performing pharmacogenomic testing. Selection of a reference laboratory depends on whether a particular genotype assay is already performed by an internal healthcare organization laboratory or only available externally. Other factors for consideration are coverage of genomic variants important for your patient population, technical support, and cost...
July 12, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28698977/pharmacogenetics-and-pharmacogenomics-of-targeted-therapeutics-in-chronic-myeloid-leukemia
#14
REVIEW
Aritro Nath, Jacqueline Wang, R Stephanie Huang
The advent of targeted therapeutics has greatly improved outcomes of chronic myeloid leukemia (CML) patients. Despite increased efficacy and better clinical responses over cytotoxic chemotherapies, many patients receiving targeted drugs exhibit a poor initial response, develop drug resistance, or undergo relapse after initial success. This inter-individual variation in response has heightened the interest in studying pharmacogenetics and pharmacogenomics (PGx) of cancer drugs. In this review, we discuss the influence of various germline and somatic factors on targeted drug response in CML...
July 11, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28696420/a-cost-effectiveness-analysis-of-maternal-cyp2d6-genetic-testing-to-guide-treatment-for-postpartum-pain-and-avert-infant-adverse-events
#15
M E Moretti, D F Lato, H Berger, G Koren, S Ito, W J Ungar
Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine. Pharmacogenetic testing may be a valuable tool to identify such mothers, but testing can be costly. The objective of the study was to determine the incremental costs of genotyping to avert neonatal adverse events during maternal pharmacotherapy. A cost-effectiveness analysis, using a decision model, was performed with a hypothetical cohort of prenatal subjects...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28696419/associations-between-the-c677t-and-a1298c-polymorphisms-of-mthfr-and-the-toxicity-of-methotrexate-in-childhood-malignancies-a-meta-analysis
#16
C Zhu, Y W Liu, S Z Wang, X L Li, X L Nie, X T Yu, L B Zhao, X L Wang
As a common chemotherapy drug, methotrexate (MTX) has achieved remarkable clinical success. However, high inter-individual variability and unpredictable toxicity continue to challenge its use in clinical practices. Some studies suggest this variation is associated with a methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, but results remain unclear. In this meta-analysis, we include 14 studies that focus on MTHFR C677T and A1298C polymorphisms in pediatric patients with malignancy. We found significant associations of the MTHFR C677T polymorphism with hepatotoxicity (grade ⩾2; CC vs CT/TT: risk ratio (RR): 0...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28696418/associations-between-functional-polymorphisms-and-response-to-biological-treatment-in-danish-patients-with-psoriasis
#17
N D Loft, L Skov, L Iversen, R Gniadecki, T N Dam, I Brandslund, H J Hoffmann, M R Andersen, R B Dessau, A C Bergmann, N M Andersen, P S Andersen, S Bank, U Vogel, V Andersen
Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28696417/harnessing-low-density-lipoprotein-receptor-protein-6-lrp6-genetic-variation-and-wnt-signaling-for-innovative-diagnostics-in-complex-diseases
#18
REVIEW
Z-M Wang, J-Q Luo, L-Y Xu, H-H Zhou, W Zhang
Wnt signaling regulates a broad variety of processes in both embryonic development and various diseases. Recent studies indicated that some genetic variants in Wnt signaling pathway may serve as predictors of diseases. Low-density lipoprotein receptor protein 6 (LRP6) is a Wnt co-receptor with essential functions in the Wnt/β-catenin pathway, and mutations in LRP6 gene are linked to many complex human diseases, including metabolic syndrome, cancer, Alzheimer's disease and osteoporosis. Therefore, we focus on the role of LRP6 genetic polymorphisms and Wnt signaling in complex diseases, and the mechanisms from mouse models and cell lines...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28696416/cytochrome-p450-interactions-are-common-and-consequential-in-massachusetts-hospital-discharges
#19
T H McCoy, V M Castro, A Cagan, L Snapper, A Roberson, R H Perlis
Despite the recognition that drug-drug interactions contribute substantially to preventable health-care costs, the prevalence of such interactions related to the cytochrome P450 system in clinical practice remains poorly characterized. This study drew retrospective hospital discharge cohorts from a large health claims data set and a large health system data set. For every hospital discharge, frequency of co-occurrence of substrates and inducers or inhibitors at cytochrome P450 2D6, 2C19, 3A4 and 1A2 were determined...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28696415/genome-wide-association-studies-of-placebo-and-duloxetine-response-in-major-depressive-disorder
#20
M Maciukiewicz, V S Marshe, A K Tiwari, T M Fonseka, N Freeman, J L Kennedy, S Rotzinger, J A Foster, S H Kennedy, D J Müller
We investigated variants associated with treatment response in depressed patients treated with either the antidepressant duloxetine or placebo using a genome-wide approach. Our sample (N=391) included individuals aged 18-75 years, diagnosed with major depressive disorder and treated with either duloxetine or placebo for up to 8 weeks. We conducted genome-wide associations for treatment response as operationalized by percentage change in Montgomery-Åsberg Depression Rating Scale score from baseline, as well as mixed models analyses across five time points...
July 11, 2017: Pharmacogenomics Journal
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