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Pharmacogenetics

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https://www.readbyqxmd.com/read/29450233/pharmacogenomics-guided-policy-in-opioid-use-disorder-oud-management-an-ethnically-diverse-case-based-approach
#1
Earl B Ettienne, Edwin Chapman, Mary Maneno, Adaku Ofoegbu, Bradford Wilson, Beverlyn Settles-Reaves, Melissa Clarke, Georgia Dunston, Kevin Rosenblatt
Introduction: Opioid use disorder (OUD) is characterized by a problematic pattern of opioid use leading to clinically-significant impairment or distress. Opioid agonist treatment is an integral component of OUD management, and buprenorphine is often utilized in OUD management due to strong clinical evidence for efficacy. However, interindividual genetic differences in buprenorphine metabolism may result in variable treatment response, leaving some patients undertreated and at increased risk for relapse...
December 2017: Addictive Behaviors Reports
https://www.readbyqxmd.com/read/29449330/therapeutic-lowering-of-lipoprotein-a-a-role-for-pharmacogenetics
#2
EDITORIAL
Michael B Boffa, Marlys L Koschinsky
No abstract text is available yet for this article.
February 2018: Circ Genom Precis Med
https://www.readbyqxmd.com/read/29443789/polymorphisms-of-drug-metabolizing-enzyme-cyp2e1-in-chinese-uygur-population
#3
Linhao Zhu, Yongjun He, Fanglin Niu, Mengdan Yan, Jing Li, Dongya Yuan, Tianbo Jin
Pharmacogenetics is the genetic basis of pharmacokinetics, genetic testing, and clinical management in diseases. Evaluation about genetic alterations of drug metabolizing enzymes in human genome contributes toward understanding the interindividual and interethnic variability for clinical response to potential toxicants. CYP2E1 gene encodes a drug-metabolizing enzyme that metabolizes mostly small, polar molecules, including toxic laboratory chemicals. The aim of this study was to investigate CYP2E1 polymorphisms and gene profile in a Chinese Uygur population...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29436624/clinical-verification-of-lou-type-warfarin-pharmacokinetic-dosing-algorithms-equation
#4
Jiangang Jiang, Ningning Ji, Jingliang Lan, Xiaoping Ge, Xiaoma Du
Warfarin is the most commonly used oral anti-coagulant in clinic practice. However, it is difficult to recommend the correct dosage due to its narrow therapeutic window. The aim of the present study was to verify the clinical value of the Lou type equation, using pharmacogenetics‑based warfarin dosing algorithms to appropriately predict the actual maintenance dose. A total of 87 Chinese Han patients who required treatment with warfarin were enrolled and randomly divided into the experimental and control groups...
February 6, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29436156/cytochrome-p450-genetic-variation-associated-with-tamoxifen-biotransformation-in-american-indian-and-alaska-native-people
#5
Burhan A Khan, Renee Robinson, Alison E Fohner, LeeAnna I Muzquiz, Brian D Schilling, Julie A Beans, Matthew J Olnes, Laura Trawicki, Holly Frydenlund, Cindi Laukes, Patrick Beatty, Brian Phillips, Deborah Nickerson, Kevin Howlett, Denise A Dillard, Timothy A Thornton, Kenneth E Thummel, Erica L Woodahl
Despite evidence that pharmacogenetics can improve tamoxifen pharmacotherapy, there are few studies with American Indian and Alaska Native (AIAN) people. We examined variation in cytochrome P450 (CYP) genes (CYP2D6, CYP3A4, CYP3A5, and CYP2C9) and tamoxifen biotransformation in AIAN patients with breast cancer (n = 42) from the Southcentral Foundation in Alaska and the Confederated Salish and Kootenai Tribes in Montana. We tested for associations between CYP diplotypes and plasma concentrations of tamoxifen and metabolites...
February 13, 2018: Clinical and Translational Science
https://www.readbyqxmd.com/read/29435984/economics-of-pharmacogenetic-guided-treatments-underwhelming-or-overstated
#6
Dyfrig A Hughes
Economic evaluations have dispelled a perception that precision medicine, achieved through pharmacogenetic testing, reduces healthcare costs. For many tests aimed at preventing adverse drug reactions, cost-effectiveness analyses predict modest improvements in health benefits and increases in total costs. While there are many uncertainties in estimating the value of testing, factors that influence cost-effectiveness include the rarity of the outcome, the effectiveness of alternative treatments, and the scope and perspective of analysis...
February 13, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29431853/rs294775-is-a-cis-regulatory-snp-for-human-ugt2b10
#7
Ji Ruan, Yu-Chen Yang, Fu-Quan Long, Chang Sun
UGT2B10 is an important metabolism enzyme in human body and its substrates include multiple amine-containing compounds, especially nicotine, tamoxifen and multiple antidepressants. Multiple common SNPs have been observed in its promoter region, but their role in expression regulation has never been investigated. In this preliminary study, we identified a novel cis-regulatory SNP, rs294775, for UGT2B10 by plasmid construction, mutagenesis, and luciferase assay, whose mechanism was also investigated. Our work provides a basis for further pharmacogenetics study...
February 12, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29429869/pharmacogenetic-decision-support-tools-a-new-paradigm-for-late-life-depression
#8
REVIEW
Ryan Abbott, Donald D Chang, Harris A Eyre, Chad A Bousman, David A Merrill, Helen Lavretsky
Clinicians still employ a "trial-and-error" approach to optimizing treatment regimens for late-life depression (LLD). With LLD affecting a significant and growing segment of the population, and with only about half of older adults responsive to antidepressant therapy, there is an urgent need for a better treatment paradigm. Pharmacogenetic decision support tools (DSTs), which are emerging technologies that aim to provide clinically actionable information based on a patient's genetic profile, offer a promising solution...
May 25, 2017: American Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/29422864/clinical-pharmacogenetic-models-of-treatment-response-to-methotrexate-monotherapy-in-slovenian-and-serbian-rheumatoid-arthritis-patients-differences-in-patient-s-management-may-preclude-generalization-of-the-models
#9
Barbara Jenko, Matija Tomšič, Biljana Jekić, Vera Milić, Vita Dolžan, Sonja Praprotnik
Objectives: Methotrexate (MTX) is the first line treatment for rheumatoid arthritis (RA), but nevertheless 30% of patients experience MTX inefficacy. Our aim was to develop a clinical pharmacogenetic model to predict which RA patients will not respond to MTX monotherapy. We also assessed whether this model can be generalized to other populations by validating it on a group of Serbian RA patients. Methods: In 110 RA Slovenian patients, data on clinical factors and 34 polymorphisms in MTX pathway were analyzed by Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression to select variables associated with the disease activity as measured by Disease Activity Score (DAS28) score after 6 months of MTX monotherapy...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29416861/prevalence-and-management-of-intrathecal-morphine-induced-pruritus-in-new-zealand-m%C3%A4-ori-healthcare-recipients
#10
Jennifer M Woods, Anecita Gigi Lim
Aims and objectives: The aim of this article was to determine whether the incidence of intrathecal morphine-induced pruritus (ITMI) was influenced by ethnicity, age or gender in relation to orthopaedic versus caesarean surgeries. Background: The use of intrathecal morphine for patients undergoing total hip and knee joint replacements and for lower segment caesarean sections (LSCS) has gained popularity worldwide since its introduction over 30 years ago. Several international studies show that morphine delivered via the intrathecal route is an effective and safe method of pain relief...
February 2018: British Journal of Pain
https://www.readbyqxmd.com/read/29413077/depression-and-pharmacogenetics
#11
David Nana Ampong
Depression is the most common and leading devastating psychiatric illness that affects a majority of the world population. The treatment of depression has been a challenge for a majority of patients and healthcare practitioners. The advent of pharmacogenomics (PGx) empowered the Food and Drug Administration to approve some antidepressant biomarkers for PGx model of treatment. The PGx testing identifies whether an individual is a poor metabolizer, ultra/rapid metabolizer, intermediate metabolizer, or essential metabolizer of an antidepressants before prescription...
February 2018: Archives of Psychiatric Nursing
https://www.readbyqxmd.com/read/29412111/efficacy-of-p2y12-receptor-blockers-after-myocardial-infarction-and-genetic-variability-of-their-metabolic-pathways
#12
Jan Machal, Ota Hlinomaz
BACKGROUND: Various antiplatelet drugs are used following acute coronary syndromes (ACS). Of them, adenosine diphosphate receptor P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor are currently used for post-ACS long-term treatment. Although they act on the same receptor, they differ in pharmacodynamics and pharmacokinetics. Several enzymes and transporters involved in the metabolism of P2Y12 inhibitors show genetic variability with functional impact. This includes P-glycoprotein, carboxylesterase 1 and, most notably, CYP2C19 that is important in clopidogrel activation...
February 5, 2018: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29411706/-maternal-bonding-style-cholinergic-receptor-gene-polymorphisms-in-association-with-smoking-related-depressive-symptoms
#13
Iren Csala, Peter Dome, Judit Lazary
Backgorund: There is accumulating evidence on the association between the cholinergic system and nicotine dependence (ND) in the literature and the bidirectional relationship of ND and depression. However, the molecular background of the development of ND and related affective phenotype is not clear. METHODS: We recruited 255 tretament-seeking smokers into our study. For phenotyping assessments we used the Fagerstrom Nicotine Dependence Test; The Minnessotta Nicotine Withdrawal Scale; the Zung Self-Rating Depression Scale and the Parental Bonding Instrument...
December 2017: Neuropsychopharmacologia Hungarica
https://www.readbyqxmd.com/read/29408742/role-of-lh-polymorphisms-and-r-hlh-supplementation-in-gnrh-agonist-treated-art-cycles-a-cross-sectional-study
#14
Ramaraju G A, Ravikrishna Cheemakurthi, Kavitha Prathigudupu, Kavitha Lakshmi Balabomma, Madan Kalagara, Sivanarayana Thota, Muralikrishna Kota
STUDY OBJECTIVES: To investigate the effect of N312S polymorphism in the LHCGR gene as a predictive pharmacogenetic marker on clinical and embryological parameters and determining the need of r-hLH supplementation combine with r-hFSH in patients undergoing ART treatment. STUDY DESIGN: In a cross-sectional study, a retrospective analysis of women (n = 553), who underwent controlled ovarian stimulation treatment protocol was conducted during the years 2012-2014...
February 2, 2018: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/29403033/hippocampus-driven-feed-forward-inhibition-of-the-prefrontal-cortex-mediates-relapse-of-extinguished-fear
#15
Roger Marek, Jingji Jin, Travis D Goode, Thomas F Giustino, Qian Wang, Gillian M Acca, Roopashri Holehonnur, Jonathan E Ploski, Paul J Fitzgerald, Timothy Lynagh, Joseph W Lynch, Stephen Maren, Pankaj Sah
The medial prefrontal cortex (mPFC) has been implicated in the extinction of emotional memories, including conditioned fear. We found that ventral hippocampal (vHPC) projections to the infralimbic (IL) cortex recruited parvalbumin-expressing interneurons to counter the expression of extinguished fear and promote fear relapse. Whole-cell recordings ex vivo revealed that optogenetic activation of vHPC input to amygdala-projecting pyramidal neurons in the IL was dominated by feed-forward inhibition. Selectively silencing parvalbumin-expressing, but not somatostatin-expressing, interneurons in the IL eliminated vHPC-mediated inhibition...
February 5, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29402974/genetic-variability-affects-absolute-and-relative-potencies-and-kinetics-of-the-anesthetics-isoflurane-and-sevoflurane-in-drosophila-melanogaster
#16
Zachariah P G Olufs, Carin A Loewen, Barry Ganetzky, David A Wassarman, Misha Perouansky
Genetic variability affects the response to numerous xenobiotics but its role in the clinically-observed irregular responses to general anesthetics remains uncertain. To investigate the pharmacogenetics of volatile general anesthetics (VGAs), we developed a Serial Anesthesia Array apparatus to expose multiple Drosophila melanogaster samples to VGAs and behavioral assays to determine pharmacokinetic and pharmacodynamic properties of VGAs. We studied the VGAs isoflurane and sevoflurane in four wild type strains from the Drosophila Genetic Reference Panel, two commonly used laboratory strains (Canton S and w 1118 ), and a mutant in Complex I of the mitochondrial electron transport chain (ND23 60114 )...
February 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29399716/pharmacogenetics-of-post-transplant-diabetes-mellitus-in-children-with-renal-transplantation-treated-with-tacrolimus
#17
Pauline Lancia, Tiphaine Adam de Beaumais, Valéry Elie, Florentine Garaix, Marc Fila, François Nobili, Bruno Ranchin, Pascale Testevuide, Tim Ulinski, Wei Zhao, Georges Deschênes, Evelyne Jacqz-Aigrain
BACKGROUND: Post-transplant diabetes mellitus (PTDM) is a major complication of immunosuppressive therapy, with many risk factors reported in adults with renal transplantation. The objective of this study was to investigate potential non-genetic and genetic risk factors of PTDM in children with renal transplantation treated with tacrolimus. METHODS: A national database was screened for patients developing PTDM within 4 years following tacrolimus introduction. PTDM was defined as glucose disorder requiring anti-diabetic treatment...
February 4, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29399533/pathogenesis-of-thrombosis-cellular-and-pharmacogenetic-contributions
#18
REVIEW
Dileep D Monie, Emma P DeLoughery
Our understanding of thrombosis formation has evolved significantly ever since physician Rudolf Virchow proposed his "triad" theory in 1856. Modern science has elucidated the mechanisms of stasis, hypercoagulability, and endothelial dysfunction. Today, we have a firm understanding of the key molecular factors involved in the coagulation cascade and fibrinolytic system, as well as the underlying genetic influences. This knowledge of cellular and genetic contributors has been translated into diverse pharmaceutical interventions...
December 2017: Cardiovascular Diagnosis and Therapy
https://www.readbyqxmd.com/read/29392710/clinical-pharmacogenetics-implementation-consortium-guideline-for-hla-genotype-and-use-of-carbamazepine-and-oxcarbazepine-2017-update
#19
Elizabeth J Phillips, Chonlaphat Sukasem, Michelle Whirl-Carrillo, Daniel J Müller, Henry M Dunnenberger, Wasun Chantratita, Barry Goldspiel, Yuan-Tsong Chen, Bruce C Carleton, Alfred L George, Taisei Mushiroda, Teri Klein, Roseann S Gammal, Munir Pirmohamed
The variant allele HLA-B*15:02 is strongly associated with greater risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients treated with carbamazepine or oxcarbazepine. The variant allele HLA-A*31:01 is associated with greater risk of maculopapular exanthema, drug reaction with eosinophilia and systemic symptoms, and SJS/TEN in patients treated with carbamazepine. We summarize evidence from the published literature supporting these associations and provide recommendations for carbamazepine and oxcarbazepine use based on HLA genotypes...
February 2, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29389890/p450-pharmacogenetics-in-indigenous-north-american-populations
#20
REVIEW
Lindsay M Henderson, Katrina G Claw, Erica L Woodahl, Renee F Robinson, Bert B Boyer, Wylie Burke, Kenneth E Thummel
Indigenous North American populations, including American Indian and Alaska Native peoples in the United States, the First Nations, Métis and Inuit peoples in Canada and Amerindians in Mexico, are historically under-represented in biomedical research, including genomic research on drug disposition and response. Without adequate representation in pharmacogenetic studies establishing genotype-phenotype relationships, Indigenous populations may not benefit fully from new innovations in precision medicine testing to tailor and improve the safety and efficacy of drug treatment, resulting in health care disparities...
February 1, 2018: Journal of Personalized Medicine
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