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Jennifer H Barrett
No abstract text is available yet for this article.
February 15, 2019: Pharmacogenomics
Joshua Gini, Adeniyi Olagunju, Laura Dickinson, Catriona Waitt, Megan Neary, Laura J Else, Marco Siccardi, Saye Khoo
AIM: Treatment and prevention of mother-to-child transmission of HIV in pregnancy utilizes tenofovir (TFV) and emtricitabine (FTC) as NRTI backbone in combination with a third agent from a different class. We hypothesized that combined effect of pregnancy and pharmacogenetics significantly changes TFV and FTC pharmacokinetics (PK). Therefore, this study aims to evaluate the role of SNPs of transporters (ABCC2 and ABCC4) on TFV and FTC PK during pregnancy. METHOD: 61 pregnant or postpartum women on TFV and FTC were selected from a group of pregnant and postpartum Nigerian women and both SNPs and drug levels were evaluated...
February 15, 2019: Pharmacogenomics
Qing Wang, Zhi-Ping Jiang, Er-Qian Yu, Jing Zeng, Yan Zhu, Hua-Lin Cai, Miao Yan, Da-Xiong Xiang, Xie-Lan Zhao, Ping Xu, Zheng Jiao, Hoan Linh Banh
AIM: This study aimed to establish a population pharmacokinetic (PPK) model in Chinese patients with chronic myeloid leukemia, and to quantify the effects of pharmacogenetics on pharmacokinetic parameters of imatinib. METHODS: A total of 229 plasma concentrations from 170 patients were analyzed. Nonlinear mixed effect model was used to establish the PPK model. RESULTS: A one-compartment model with first-order absorption and first-order elimination adequately describes imatinib pharmacokinetics...
February 15, 2019: Pharmacogenomics
Sophie E Legge, James Tr Walters
Clozapine is the only effective antipsychotic for treatment-resistant schizophrenia but remains widely under prescribed, at least in part due to its potential to cause agranulocytosis and neutropenia. In this article, we provide an overview of the current understanding of the genetics of clozapine-associated agranulocytosis and neutropenia. We now know that the genetic etiology of clozapine-associated neutropenia is complex and is likely to involve variants from several genes including HLA-DQB1, HLA-B and SLCO1B3/SLCO1B7...
February 15, 2019: Pharmacogenomics
Anushka Naidoo, Maxwell Chirehwa, Veron Ramsuran, Helen McIlleron, Kogieleum Naidoo, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ncgapu, John Adamson, Katya Govender, Paolo Denti, Nesri Padayatchi
AIM: We report the prevalence and effect of genetic variability on pharmacokinetic parameters of isoniazid and rifampicin. MATERIALS & METHODS: Genotypes for SLCO1B1, NAT2, PXR, ABCB1 and UGT1A genes were determined using a TaqMan® Genotyping OpenArray™. Nonlinear mixed-effects models were used to describe drug pharmacokinetics. RESULTS: Among 172 patients, 18, 43 and 34% were classified as rapid, intermediate and slow NAT2 acetylators, respectively...
February 15, 2019: Pharmacogenomics
Hidenori Kamio, Toshitaka Uchiyama, Hitoshi Kanno, Yoshiko Onoe, Kayoko Saito, Shingo Kameoka, Takako Kamio, Takahiro Okamoto
AIM: The aim of this study was to identify pharmacogenomic biomarkers to predict tegafur-uracil (UFT)-induced liver dysfunction. PATIENTS & METHODS:  A total of 68 patients, who were administered UFT, were evaluated using a two-step pharmacogenomics analysis. RESULTS: The first screening revealed the association between five SNPs and UFT-induced hepatic dysfunction. In the second step, SLCO1B1 (rs4149056) was found to be the only SNP associated with UFT treatment-related elevation of aspartate aminotransferase (odds ratio: C/C vs T/T = 7...
February 8, 2019: Pharmacogenomics
Ghada M Ezzat, Ahlam B Ali, Nahed A Mohamed, Helal F Hetta
AIM: To investigate ENDRA rs5333 gene polymorphism distribution in idiopathic nephrotic syndrome (INS) and to analyze their association with response to steroid therapy, and biochemical markers of INS. SUBJECTS & METHODS: The PCR-restriction fragment length polymorphism was used to analyze ENDRA rs5333 polymorphism in 100 children with idiopathic nephrotic syndrom (INS) and 100 healthy children. Plasma endothelin-1 were measured by ELISA. RESULTS: The ENDRA rs5333 gene polymorphism was not associated with risk of INS...
January 23, 2019: Pharmacogenomics
Ying Zeng, Tai-Lin Li, Hai-Bo Zhang, Jun-Li Deng, Rui Zhang, Hong Sun, Zi-Rui Wan, Ying-Zi Liu, Yuan-Shan Zhu, Guo Wang
AIM: The present study aimed to assess the association between IGF2/H19 genetic variants and susceptibility to platinum-based chemotherapy in epithelial ovarian cancer (EOC). METHODS: A total of 43 platinum-resistant (PR) and 138 platinum-sensitive (PS) EOC patients were recruited in our study. Twenty-one polymorphisms in IGF2/H19 locus were genotyped by Sequenom MassARRAY assay. RESULTS: The frequencies of GG genotype in both rs3842761(C/G) and rs4244809(A/G) were significantly lower in PR group compared with those in PS group (9...
January 23, 2019: Pharmacogenomics
Guangyan Mu, Qian Xiang, Shuang Zhou, Qiufen Xie, Zhiyan Liu, Zhuo Zhang, Yimin Cui
AIM: Genetic polymorphisms may influence the incidence of angiotensin-converting enzyme (ACE) inhibitor-induced cough. This study aims to investigate this association. METHODS: Ten electronic databases and PharmGKB were systematically searched. Pooled odds ratio values and their 95% CI were used to assess the association, using the random-effects model. RESULTS: A total of 26 studies were included in the review, 17 of them were included from two separated meta-analysis (ACE I/D or BDKRB2-58T/C)...
January 23, 2019: Pharmacogenomics
Allyson N Hamlin, Joseph Tillotson, Namandjé N Bumpus
As antiretroviral therapy has become more accessible across the world and coformulations have improved patient compliance; the morbidity and mortality of HIV/AIDS has decreased. However, there is still a substantial gap in knowledge regarding the impact of genetic variation on the metabolism of and response to some of the most commonly prescribed antiretrovirals, including the nucleotide reverse transcriptase inhibitor tenofovir. While it has been scientifically established that tenofovir must be activated to be efficacious against HIV, the enzymes responsible for this activation have not been well characterized...
January 10, 2019: Pharmacogenomics
XiaoXia Wei, JiaQin Cai, Hong Sun, Na Li, Chenxia Xu, Guifeng Zhang, Yuxia Sui, Jie Zhuang, Bin Zheng
AIM: To assess the cost-effectiveness of UGT1A1*6/*28 genotyping compared with no genotyping or no dose adjustment before irinotecan administration in China. MATERIALS & METHODS: A decision tree model was developed to evaluate costs and health outcomes represented as quality-adjusted life years gained. Model inputs for the frequency of genotypes, the probability of neutropenia under FOLFIRI chemotherapy and direct costs and utilities were obtained from published sources...
January 10, 2019: Pharmacogenomics
Jiancheng Su, Shaolin Ruan, Shengkun Dai, Jing Mi, Wei Chen, Songshan Jiang
AIM: Neurofibromatosis type 1 (NF1) loss confers chemoresistance in multiple cancers. However, the etiology remains largely unknown. Our study aimed to scrutinize the role of NF1 in chemoresistant ovarian cancer and its underlying mechanism. MATERIALS & METHODS: 4',6-diamidino-2-phenylindole staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, luciferase reporter assay, chromatin immunoprecipitation, Western blot, quantitative real-time-PCR and rescue experiments were performed to illustrate the antiapoptotic role of NF1 loss and its underlying mechanism...
December 13, 2018: Pharmacogenomics
Tomas Zemanek, Bohuslav Melichar, Martin Lovecek, Pavel Soucek, Beatrice Mohelnikova-Duchonova
Pancreatic carcinoma is usually diagnosed late when treatment options are limited and is considered a chemo-resistant malignancy. However, early stage, good performance status and specific patient subgroup are thought to have a more favorable prognosis. Search for novel molecular biomarkers, which could predict treatment resistance, represents a major opportunity, but also a challenge in further research. This review summarizes most aspects of individualized therapy of pancreatic cancer including promising biomarkers, BRCA-deficient pancreatic cancer and its etiology...
December 12, 2018: Pharmacogenomics
Chad A Bousman, Katarina Arandjelovic, Serafino G Mancuso, Harris A Eyre, Boadie W Dunlop
AIM: To conducted a systematic review and meta-analysis of prospective, randomized controlled trials (RCTs) that examined pharmacogenetic-guided decision support tools (DSTs) relevant to depressive symptom remission in major depressive disorder (MDD). PATIENTS & METHODS: Random-effects meta-analysis was performed on RCTs that examined the effect of DSTs on remission rates in MDD. RCT quality was assessed using the Cochrane Collaboration Criteria. RESULTS & CONCLUSION: A total of 1737 eligible subjects from five RCTs were examined...
December 6, 2018: Pharmacogenomics
Lauren A Marcath, Kelley M Kidwell, Adam C Robinson, Kiran Vangipuram, Monika L Burness, Jennifer J Griggs, Catherine Van Poznak, Anne F Schott, Daniel F Hayes, Norah Lynn Henry, Daniel L Hertz
AIM:  First, evaluate if patients carrying putatively diminished activity CYP2C8 genotype have longer paclitaxel exposure (e.g., time above threshold concentration of 0.05 μM [Tc >0.05 ]). Second, screen additional pharmacogenes for associations with Tc >0.05 . Methods: Pharmacogene panel genotypes were translated into genetic phenotypes for associations with Tc >0.05 (n = 58). RESULTS: Patients with predicted low-activity CYP2C8 had shorter Tc >0...
December 6, 2018: Pharmacogenomics
Teresa T Ho, Sheeba Varghese Gupta, Amarilis Sanchez-Valle
Clonazepam undergoes nitroreduction to 7-amino-clonazepam via CYP3A4/5, followed by acetylation to 7-acetamido-clonazepam via N-acetyltransferase-2 (NAT2) enzyme. While no pharmacological activity is attributed to the metabolites of clonazepam, 7-amino-clonazepam has some affinity for the benzodiazepine receptor as a partial agonist for the gamma aminobutyric acid-A receptor and can compete with clonazepam. Interindividual variability in the incidence of adverse events in patients may, in part, be attributable to differences in clonazepam metabolism...
December 6, 2018: Pharmacogenomics
Eleonora Rofi, Caterina Vivaldi, Marzia Del Re, Elena Arrigoni, Stefania Crucitta, Niccola Funel, Stefano Fogli, Enrico Vasile, Gianna Musettini, Lorenzo Fornaro, Alfredo Falcone, Romano Danesi
Circulating tumor DNA, circulating tumor cells and tumor-related exosomes may offer new opportunities to provide insights into the biological and clinical characteristics of a neoplastic disease. They represent alternative routes for diagnostic and prognostic purposes, and for predicting and longitudinally monitoring response to treatment and disease progression. Hence, circulating biomarkers represent promising noninvasive tools in the scenario of pancreatic cancer, where neither molecular nor clinical predictors of treatment benefit have been identified yet...
December 6, 2018: Pharmacogenomics
Yong Han, Hong Zhou, Jie Cai, Jun Huang, Jing Zhang, Shao-Jun Shi, Ya-Ni Liu, Yu Zhang
AIM: The aim of this study was to evaluate tacrolimus population pharmacokinetics and investigate factors that explain tacrolimus variability in adult heart transplant patients. METHODS: A total of 707 tacrolimus concentrations from 107 adult heart transplant patients were included in model development. The effects of demographic, clinical factors and CYP3A5 genotype on tacrolimus clearance were evaluated using a nonlinear mixed-effects modeling. 24 patients with 106 tacrolimus concentrations were used for external validation...
January 2019: Pharmacogenomics
Wanqiong Qiao, Suparna Martis, Geetu Mendiratta, Lisong Shi, Mariana R Botton, Yao Yang, Andrea Gaedigk, Raymon Vijzelaar, Lisa Edelmann, Ruth Kornreich, Robert J Desnick, Stuart A Scott
AIM: To comprehensively interrogate CYP2D6 by integrating genotyping, copy number analysis and novel strategies to identify CYP2D6*36 and characterize CYP2D6 duplications. METHODS: Genotyping of 16 CYP2D6 alleles, multiplex ligation-dependent probe amplification (MLPA) and CYP2D6*36 and duplication allele-specific genotyping were performed on 427 African-American, Asian, Caucasian, Hispanic, and Ashkenazi Jewish individuals. RESULTS: A novel PCR strategy determined that almost half of all CYP2D6*10 (100C>T) alleles are actually *36 (isolated or in tandem with *10) and all identified duplication alleles were characterized...
January 2019: Pharmacogenomics
Sarah Jones
No abstract text is available yet for this article.
January 2019: Pharmacogenomics
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