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Pharmacogenomics

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https://www.readbyqxmd.com/read/28358601/pharmacogenetics-in-the-treatment-of-pre-eclampsia-current-findings-challenges-and-perspectives
#1
Marcelo R Luizon, Ana Ct Palei, Ricardo C Cavalli, Valeria C Sandrim
Pre-eclampsia (PE) is defined as pregnancy-induced hypertension and proteinuria, and is a major cause of maternal and perinatal morbidity and mortality. A large subgroup of pregnant women with PE is nonresponsive to antihypertensive drugs, including methyldopa, nifedipine and hydralazine. Pharmacogenomics may help to guide the individualized therapy for this nonresponsive subgroup. However, just a few pharmacogenetic studies examined the effects of genetic polymorphisms on response to antihypertensive drugs in PE, and the criteria of responsiveness used to define responsive or nonresponsive subgroups to antihypertensive therapy should be replicated by others...
March 30, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28358597/common-genetic-polymorphisms-of-adenosine-a2a-receptor-do-not-influence-response-to-regadenoson
#2
Mark Berlacher, Ronald Mastouri, Santosh Philips, Todd C Skaar, Rolf P Kreutz
AIM: Hemodynamic response to regadenoson varies greatly, and underlying mechanisms for variability are poorly understood. We hypothesized that five common variants of adenosine A2A receptor (ADORA2A) are associated with altered response to regadenoson. METHODS: Consecutive subjects (n = 357) undergoing resting regadenoson nuclear stress imaging were enrolled. Genotyping was performed using Taqman-based assays for rs5751862, rs229838, rs3761422, rs2267076 and rs5751876...
March 30, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28353407/replicated-evidence-for-aminoacylase-3-and-nephrin-gene-variations-to-predict-antihypertensive-drug-responses
#3
Jenni M Rimpelä, Kimmo K Kontula, Frej Fyhrquist, Kati M Donner, Annukka M Tuiskula, Antti-Pekka Sarin, Robert P Mohney, Steven M Stirdivant, Timo P Hiltunen
AIM: To replicate the genome-wide associations of the antihypertensive effects of bisoprolol and losartan in GENRES, using the Finnish patients of LIFE study. PATIENTS & METHODS: We analyzed association of four SNPs with atenolol and three SNPs with losartan response in 927 Finnish LIFE patients (467 for atenolol and 460 for losartan). RESULTS: rs2514036, a variation at a transcription start site of ACY3, was associated with blood pressure response to atenolol in men in LIFE...
March 29, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28350522/the-influences-of-slco1b1-and-abcb1-genotypes-on-the-pharmacokinetics-of-simvastatin-in-relation-to-cyp3a4-inhibition
#4
Fen Jiang, Jong-Yeol Choi, Ju-Hyun Lee, Sunae Ryu, Ze-Won Park, Jong-Gu Lee, Han-Sung Na, Seok-Yong Lee, Woo-Yong Oh, Myeon-Woo Chung, Seung-Eun Choi
AIM: To investigate the combined effects of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin and its active metabolite simvastatin acid, in relation to CYP3A4 inhibition. METHODS: We conducted a single-dose pharmacokinetic study of simvastatin in 26 healthy volunteers screened for their SLCO1B1 c.521T>C and ABCB1 c.1236C>T-2677G>T-3435C>T genotypes, with and without amlodipine pretreatment. The genetic effects and drug-interaction effect on simvastatin pharmacokinetic parameters were analyzed using a linear-mixed model...
March 28, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28346074/germline-genetic-predictors-of-aromatase-inhibitor-concentrations-estrogen-suppression-and-drug-efficacy-and-toxicity-in-breast-cancer-patients
#5
Daniel L Hertz, N Lynn Henry, James M Rae
The third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, are highly effective for the treatment of estrogen receptor-positive breast cancer in postmenopausal women. AIs inhibit the aromatase (CYP19A1)-mediated production of estrogens. Most patients taking AIs achieve undetectable blood estrogen concentrations resulting in drug efficacy with tolerable side effects. However, some patients have suboptimal outcomes, which may be due, in part, to inherited germline genetic variants...
March 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28346059/deferasirox-pharmacogenetic-influence-on-pharmacokinetic-efficacy-and-toxicity-in-a-cohort-of-pediatric-patients
#6
Sarah Allegra, Silvia De Francia, Jessica Cusato, Arianna Arduino, Davide Massano, Filomena Longo, Antonio Piga, Antonio D'Avolio
AIM: We aimed to evaluate the influence of genetic polymorphisms involved in deferasirox metabolism and transport on its pharmacokinetics and treatment toxicity, in a cohort of β-thalassaemic children. PATIENTS & METHODS: Drug plasma concentrations were measured by a HPLC-UV method. Allelic discrimination for UGT1A1, UGT1A3, CYP1A1, CYP1A2, CYP2D6, MRP2 and BCRP1 polymorphisms was performed by real-time PCR. RESULTS: CYP1A1 rs2606345AA influenced Ctrough (p = 0...
March 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28346058/promising-pharmacogenetic-targets-for-treating-alcohol-use-disorder-evidence-from-preclinical-models
#7
Jennifer A Rinker, Patrick J Mulholland
Inherited genetic variants contribute to risk factors for developing an alcohol use disorder, and polymorphisms may inform precision medicine strategies for treating alcohol addiction. Targeting genetic mutations linked to alcohol phenotypes has provided promising initial evidence for reducing relapse rates in alcoholics. Although successful in some studies, there are conflicting findings and the reports of adverse effects may ultimately limit their clinical utility, suggesting that novel pharmacogenetic targets are necessary to advance precision medicine approaches...
March 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28346057/the-role-of-germline-variants-in-chemotherapy-outcome-in-brain-tumors-a-systematic-review-of-pharmacogenetic-studies
#8
Marije J Klumpers, Marieke Jh Coenen, Corrie Em Gidding, D Maroeska Wm Te Loo
AIM: This systematic review provides an overview of publications concerning pharmacogenetic research in pediatric patients with medulloblastoma and low-grade glioma. MATERIALS & METHODS: Three electronic databases searches including a manual search were performed to identify studies investigating potential interactions between germline variants and chemotherapy efficacy and toxicity. RESULTS: Out of 3570 citations, 21 studies were included...
March 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28290774/multimorbidity-polypharmacy-and-pharmacogenomics-in-old-age
#9
Jürgen Brockmöller, Julia C Stingl
No abstract text is available yet for this article.
March 14, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28290771/institutional-profile-pharmacogenomic-research-in-r-stephanie-huang-laboratory
#10
Paul Geeleher, Aritro Nath, Rong Stephanie Huang
The Huang Lab was established in 2009 at the University of Chicago and has since been active in conducting pharmacogenomic research. Our laboratory's main research focus is translational pharmacogenomics with a particular interest in the pharmacogenomics of anticancer agents. By systematically evaluating the human genome and its relationships to drug response and toxicity, our goal is to develop clinically useful models that predict risk for adverse drug reactions and nonresponse prior to administration of chemotherapy...
March 14, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28290770/in-vivo-characterization-of-cyp2d6-12-29-and-84-using-dextromethorphan-as-a-probe-drug-a-case-report
#11
Andrea Gaedigk, Greyson P Twist, Emily G Farrow, Jennifer A Lowry, Sarah E Soden, Neil A Miller
CYP2D6*84 was first described in a Black South African subject, however, its function remains unknown. Astrolabe, a probabilistic scoring tool developed in our laboratory to call genotypes from whole genome sequence, identified CYP2D6*84 in a trio. The father presented with intermediate metabolism when challenged with the CYP2D6 probe drug dextromethorphan (DM/dextrorphan [DX] = 0.0839). Since his second allele, CYP2D6*12, is nonfunctional, the observed activity is derived by CYP2D6*84. This finding suggests that the allele's hallmark P267H causes decreased activity toward DM and that this allele should receive a value of 0...
March 14, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28290769/sequencing-brain-metastases-and-opportunities-for-targeted-therapies
#12
Ugonma N Chukwueke, Priscilla K Brastianos
CNS metastases have long been recognized as a common and late complication of systemic malignancies. They represent the most common tumor of the brain. As outcomes and overall survival improve with better tolerated and more durable responses from therapies for systemic cancers, the incidence and prevalence of brain metastases is likely to increase. Among the most common systemic cancers leading to brain metastases include lung, melanoma, breast (triple-negative histology) and renal cell cancers. To date, there has been infrequent involvement of gastrointestinal and gynecologic malignancies; however, this may also change, reflecting improvement in overall survival and therapeutic regimens...
March 14, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28350251/impact-of-cyp2d6-genotype-on-amitriptyline-efficacy-for-the-treatment-of-diabetic-peripheral-neuropathy-a-pilot-study
#13
Mamoonah Chaudhry, Marco Alessandrini, Jacobus Rademan, Tyren M Dodgen, Francois E Steffens, Danie G van Zyl, Andrea Gaedigk, Michael S Pepper
AIM: Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles. METHOD: To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced...
April 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28346084/is-there-a-role-for-pharmacogenetics-in-the-dosing-of-fentanyl
#14
Stijn Lw Koolen, Carin Cd Van der Rijt
No abstract text is available yet for this article.
April 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28346068/institutional-profile-university-of-florida-health-personalized-medicine-program
#15
Larisa H Cavallari, Kristin W Weitzel, Amanda R Elsey, Xinyue Liu, Scott A Mosley, Donald M Smith, Benjamin J Staley, Almut G Winterstein, Carol A Mathews, Francesco Franchi, Fabiana Rollini, Dominick J Angiolillo, Petr Starostik, Michael J Clare-Salzler, David R Nelson, Julie A Johnson
The University of Florida (UF) Health Personalized Medicine Program launched in 2012 with CYP2C19 genotyping for clopidogrel response at UF Health Shands Hospital. We have since expanded CYP2C19 genotyping to UF Health Jacksonville and established the infrastructure at UF Health to support clinical implementation for five additional gene-drug pairs: TPMT-thiopurines, IFNL3 (IL28B)-PEG IFN-α-based regimens, CYP2D6-opioids, CYP2D6/CYP2C19-antidepressants and CYP2C19-proton pump inhibitors. We are contributing to the evidence based on outcomes with genotype-guided therapy through pragmatic studies of our clinical implementations...
April 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28346060/stem-cell-derived-neurons-in-the-development-of-targeted-treatment-for-schizophrenia-and-bipolar-disorder
#16
Bradley Watmuff, Bangyan Liu, Rakesh Karmacharya
The recent advent of induced pluripotent stem cells has enabled the study of patient-specific and disease-related neurons in vitro and has facilitated new directions of inquiry into disease mechanisms. With these approaches, we now have the possibility of correlating ex vivo cellular phenotypes with individual patient response to treatment and/or side effects, which makes targeted treatments for schizophrenia and bipolar disorder a distinct prospect in the coming years. Here, we briefly review the current state of stem cell-based models and explore studies that are providing new insights into the disease biology of schizophrenia and bipolar disorder, which are laying the foundations for the development of novel targeted therapies...
April 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28290747/clinicians-perceptions-of-pharmacogenomics-use-in-psychiatry
#17
Christopher Yi Wen Chan, Boon Yiang Chua, Mythily Subramaniam, Emily Liew Kai Suen, Jimmy Lee
AIM: This study aims to assess the attitudes and opinions of clinicians practicing in psychiatry toward pharmacogenomic testing, and in so doing elicits possible barriers and risks to employ this technology in patient care. MATERIALS & METHODS: Doctors and pharmacists presently practicing in psychiatry were invited to participate in an anonymous web-based survey. Besides information on participant characteristics and experience in psychiatry, specific themes on pharmacogenomics including self-assessed competency, perceived usefulness in clinical situations, perceived risks and preferred mode of education were evaluated...
April 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28244813/pharmacogenomics-of-autism-spectrum-disorder
#18
Jacob T Brown, Seenae Eum, Edwin H Cook, Jeffrey R Bishop
Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and interactions as well as restricted, repetitive behaviors and interests. Pharmacologic interventions are often needed to manage irritability, aggressive behaviors and hyperactivity. Pharmacogenomic studies have investigated genetic associations with treatment response and side effects in an attempt to better understand drug mechanisms in hopes of optimizing the balance of symptom improvement versus side effects...
March 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28244812/primary-care-providers-use-of-pharmacist-support-for-delivery-of-pharmacogenetic-testing
#19
Susanne B Haga, Rachel Mills, Jivan Moaddeb, Nancy Allen LaPointe, Alex Cho, Geoffrey S Ginsburg
AIM: To investigate provider utilization of pharmacist support in the delivery of pharmacogenetic testing in a primary care setting. METHODS: Two primary care clinics within Duke University Health System participated in the study between December 2012 and July 2013. One clinic was provided with an in-house pharmacist and the second clinic had an on-call pharmacist. RESULTS: Providers in the in-house pharmacist arm consulted with the pharmacist for 13 of 15 cases, or about one of every four patients tested compared with one of every 7...
March 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28244811/systematic-screening-for-cyp3a4-genetic-polymorphisms-in-a-han-chinese-population
#20
Guo-Xin Hu, Da-Peng Dai, Hao Wang, Xiang-Xin Huang, Xiao-Yang Zhou, Jie Cai, Hao Chen, Jian-Ping Cai
AIM: To systematically investigate the genetic polymorphisms of the CYP3A4 gene in a Han Chinese population. MATERIALS & METHODS: The promoter and exons of CYP3A4 gene in 1114 unrelated, healthy Han Chinese subjects were amplified and genotyped by direct sequencing. RESULTS: In total, five previously reported alleles (*1G, *4, *5, *18B and *23) were detected, of which one allele (*23) was reported for the first time in Han Chinese population...
March 2017: Pharmacogenomics
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