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Pharmacogenetic

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https://www.readbyqxmd.com/read/28921760/genome-wide-association-study-of-a-nicotine-metabolism-biomarker-in-african-american-smokers-impact-of-chromosome-19-genetic-influences
#1
Meghan J Chenoweth, Jennifer J Ware, Andy Z X Zhu, Christopher B Cole, Lisa Sanderson Cox, Nikki Nollen, Jasjit S Ahluwalia, Neal L Benowitz, Robert A Schnoll, Larry W Hawk, Paul M Cinciripini, Tony P George, Caryn Lerman, Joanne Knight, Rachel F Tyndale
BACKGROUND AND AIMS: The activity of CYP2A6, the major nicotine-inactivating enzyme, is measurable in smokers using the nicotine metabolite ratio (NMR; 3'hydroxycotinine/cotinine). Due to its role in nicotine clearance, the NMR is associated with smoking behaviours and response to pharmacotherapies. The NMR is highly heritable (~80%), and on average lower in African Americans (AA) versus Whites. We previously identified several reduce and loss-of-function CYP2A6 variants common in individuals of African descent...
September 16, 2017: Addiction
https://www.readbyqxmd.com/read/28921458/pharmacogenetics-and-pharmacogenomics-in-moderate-to-severe-psoriasis
#2
REVIEW
María C Ovejero-Benito, Ester Muñoz-Aceituno, Alejandra Reolid, Miriam Saiz-Rodríguez, Francisco Abad-Santos, Esteban Daudén
Pharmacogenetics is the study of variations in DNA sequence related to drug response. Moreover, the evolution of biotechnology and the sequencing of human DNA have allowed the creation of pharmacogenomics, a branch of genetics that analyzes human genes, the RNAs and proteins encoded by them, and the inter-and intra-individual variations in expression and function in relation to drug response. Pharmacogenetics and pharmacogenomics are being used to search for biomarkers that can predict response to systemic treatments, including those for moderate-to-severe psoriasis...
September 18, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28919802/abcb1-and-abcc1-single-nucleotide-polymorphisms-in-patients-treated-with-clozapine
#3
Irina Piatkov, Dorgival Caetano, Yolinda Assur, Sue Lynn Lau, Trudi Jones, Steven C Boyages, Mark McLean
Clozapine (CZ) has superior efficacy to other antipsychotic agents in the treatment of schizophrenia and has been extensively used in clinical practice. ATP-binding cassette (ABC) transporter proteins are responsible for the distribution of various molecules as well as drugs across extracellular and intracellular membranes, including the blood-brain barrier. Genetic variations in these proteins can account for differences in treatment response. We investigated the influence of ABCB1 rs1045642 and ABCC1 rs212090 single-nucleotide polymorphisms (SNPs) on CZ serum level, clinical outcome, and changes in body mass index (BMI) in the first year of CZ treatment...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28915306/cost-utility-study-of-warfarin-genotyping-in-the-vachs-affiliated-anticoagulation-clinic-of-puerto-rico
#4
Carlos Martes-Martinez, Cristian Méndez-Sepúlveda, Joel Millán-Molina, Matthew French-Kim, Heriberto Marín-Centeno, Giselle C Rivera-Miranda, José J Hernández-Muñoz, Jorge Duconge-Soler
OBJECTIVE: To evaluate the cost-utility of the pharmacogenetic-guided dosing of warfarin (PGx), when compared to the current dosing strategy. METHODS: A Markov model was developed to assess the impact of the genotypingguided warfarin dosing in a hypothetical cohort of patients. The model was based on the percentage of time patients spent within the therapeutic international normalized ratio (INR) range (PTTR). PTTR estimates and genotype distribution were derived from a cohort of patients (n = 206) treated in the Veteran Affairs Caribbean Healthcare System (VACHS) and from results of other research study...
September 2017: Puerto Rico Health Sciences Journal
https://www.readbyqxmd.com/read/28914446/risk-factors-for-thiopurine-induced-myelosuppression-and-infections-in-inflammatory-bowel-disease-patients-with-a-normal-tpmt-genotype
#5
M M T J Broekman, M J H Coenen, G J Wanten, C J van Marrewijk, O H Klungel, A L M Verbeek, P M Hooymans, H-J Guchelaar, H Scheffer, L J J Derijks, D R Wong, D J de Jong
BACKGROUND: Leucopenia is a common side effect in patients treated with thiopurines. Variants in the thiopurine S-methyltransferase (TPMT) gene are the best-known risk factor, but only explain up to 25% of leucopenia cases. AIM: To identify the clinical risk factors for thiopurine-induced leucopenia in patients without a common TPMT variant, and explore if these patients are at increased risk for infections. METHODS: Post hoc analysis of the Thiopurine response Optimisation by Pharmacogenetic testing in Inflammatory bowel disease Clinics (TOPIC) trial...
September 15, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28904008/mechanisms-in-endocrinology-clinical-and-pharmacogenetic-aspects-of-the-growth-hormone-receptor-polymorphism
#6
Cesar Luiz Boguszewski, Edna Jesus Litenski Barbosa, Per-Arne Svensson, Gudmundur Johannsson, Camilla A M Glad
Pharmacogenetics aims to maximize the beneficial effects of a medical therapy by identifying genetic finger prints from responders and non-responders and, thereby, improving safety and efficacy profile of the drug. Most subjects who are deficient in growth hormone (GHD) are candidates for recombinant human GH (rhGH) therapy. To date, it is well established that even after adjustments for several clinical variables, such as age, gender, body composition and the age at onset of the GHD, response to rhGH treatment is highly variable among individuals, part of which is believed to be due to genetic factors within the GH system...
September 13, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28900583/the-daniel-k-inouye-college-of-pharmacy-scripts-precision-medicine-through-the-use-of-pharmacogenomics-current-status-and-barriers-to-implementation
#7
Anita E Ciarleglio, Carolyn Ma
The precision medicine initiative brought forth by President Barack Obama in 2015 is an important step on the journey to truly personalized medicine. A broad knowledge and understanding of the implications of the pharmacogenomic literature will be critical to the achievement of this goal. While a great amount of data has been published in the areas of pharmacogenomics and pharmacogenetics, there are still relatively few instances in which the need for clinical intervention can be stated without doubt, and which are widely accepted and practiced by the medical community...
September 2017: Hawai'i Journal of Medicine & Public Health: a Journal of Asia Pacific Medicine & Public Health
https://www.readbyqxmd.com/read/28892404/mechanisms-underlying-metabolic-disturbances-associated-with-psychosis-and-antipsychotic-drug-treatment
#8
Gavin P Reynolds, Olga O McGowan
The increase in cardiovascular disease and reduced life expectancy in schizophrenia likely relate to an increased prevalence of metabolic disturbances. Such metabolic risk factors in schizophrenia may result from both symptom-related effects and aetiological factors. However, a major contributory factor is that of treatment with antipsychotic drugs. These drugs differ in effects on body weight; the underlying mechanisms are not fully understood and may vary between drugs, but may include actions at receptors associated with the hypothalamic control of food intake...
August 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28892154/pharmacogenetics-of-opioid-analgesics-in-dogs
#9
REVIEW
K Kongara
Genetic variation causes interindividual variability in drug absorption, distribution, metabolism and excretion. These pharmacokinetic processes will influence the observed efficacy and toxicity of a drug. Polymorphisms in the genes encoding the metabolizing enzymes, transport proteins and receptors have been linked to the inconsistency in responses to opioid treatment in humans and laboratory animals. Pharmacogenetics is relatively less developed field in veterinary medicine compared to significant advances in knowledge on genetic basis of variation in drug responses and clinical applications in human medicine...
September 11, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28887233/methotrexate-pharmacogenetics-in-uruguayan-adults-with-hematological-malignant-diseases
#10
Andrea Giletti, Marcelo Vital, Mariana Lorenzo, Patricia Cardozo, Gabriel Borelli, Raúl Gabus, Lem Martínez, Lilian Díaz, Rodrigo Assar, María Noel Rodriguez, Patricia Esperón
BACKGROUND: Individual variability is among the causes of toxicity and interruption of treatment in acute lymphoblastic leukemia (ALL) and severe non-Hodgkin lymphoma (NHL) patients under protocols including Methotrexate (MTX): 2,4-diamino-N10-methyl propyl-glutamic acid. METHODS: 41 Uruguayan patients were recruited. Gene polymorphisms involved in MTX pathway were analyzed and their association with treatment toxicities and outcome was evaluated. RESULTS: Genotype distribution and allele frequency were determined for SLC19A1 G80A, MTHFR C677T and A1298C, TYMS 28bp copy number variation, SLCO1B1 T521C, DHFR C-1610G/T, DHFR C-680A, DHFR A-317G and DHFR 19bp indel...
September 5, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28882537/bevacizumab-induced-hypertension-clinical-presentation-and-molecular-understanding
#11
REVIEW
Megan Li, Deanna L Kroetz
Bevacizumab is a vascular endothelial growth factor-A-specific angiogenesis inhibitor indicated as an adjunct to chemotherapy for the treatment of several types of cancer. Hypertension is commonly observed during bevacizumab treatment, and high-grade toxicity can limit therapy and lead to other cardiovascular complications. The factors that contribute to interindividual variability in blood pressure response to bevacizumab treatment are not well understood. In this review, we outline research efforts to understand the mechanisms and pathophysiology of hypertension resulting from bevacizumab treatment...
September 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28882023/apex1-polymorphism-and-mercaptopurine-related-early-onset-neutropenia-in-pediatric-acute-lymphoblastic-leukemia
#12
Hyery Kim, Heewon Seo, Yoomi Park, Byung-Joo Min, Myung-Eui Seo, Kyung Duk Park, Hee Young Shin, Ju Han Kim, Hyoung Jin Kang
Purpose: Mercaptopurine (MP) is one of the main chemotherapeutics for acute lymphoblastic leukemia (ALL). To improve treatment outcomes, constant MP dose titration is essential to maintain steady drug exposure, while minimizing myelosuppression. We performed two-stage analyses to identify genetic determinants of MP-related neutropenia in Korean pediatric ALL patients. Materials and Methods: Targeted sequencing of 40 patients who exhibited definite MP intolerance was conducted using a novel panel of 211 pharmacogenetic-related genes, and subsequent analysis was performed with 185 patients...
September 4, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28878673/review-of-the-reported-measures-of-clinical-validity-and-clinical-utility-as-arguments-for-the-implementation-of-pharmacogenetic-testing-a-case-study-of-statin-induced-muscle-toxicity
#13
REVIEW
Marleen E Jansen, T Rigter, W Rodenburg, T M C Fleur, E J F Houwink, M Weda, Martina C Cornel
Advances from pharmacogenetics (PGx) have not been implemented into health care to the expected extent. One gap that will be addressed in this study is a lack of reporting on clinical validity and clinical utility of PGx-tests. A systematic review of current reporting in scientific literature was conducted on publications addressing PGx in the context of statins and muscle toxicity. Eighty-nine publications were included and information was selected on reported measures of effect, arguments, and accompanying conclusions...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28871815/pharmacogenetics-of-aldo-keto-reductase-1c-akr1c-enzymes
#14
Osama Y Alshogran
Genetic variation in metabolizing enzymes contributes to variable drug response and disease risk. Aldo-keto reductase type 1C (AKR1C) comprises a sub-family of reductase enzymes that play critical roles in the biotransformation of various drug substrates and endogenous compounds such as steroids. Several single nucleotide polymorphisms have been reported among AKR1C encoding genes, which may affect the functional expression of the enzymes. Areas covered: This review highlights and comprehensively discusses previous pharmacogenetic reports that have examined genetic variations in AKR1C and their association with disease development, drug disposition, and therapeutic outcomes...
September 5, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28871191/pharmacogenetics-of-methylphenidate-in-childhood-attention-deficit-hyperactivity-disorder-long-term-effects
#15
Clara I Gomez-Sanchez, Juan J Carballo, Rosa Riveiro-Alvarez, Victor Soto-Insuga, Maria Rodrigo, Ignacio Mahillo-Fernandez, Francisco Abad-Santos, Rafael Dal-Ré, Carmen Ayuso
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in which a significant proportion of patients do not respond to treatment. The objective of this study was to examine the role of genetic risk variants in the response to treatment with methylphenidate (MPH). The effectiveness of MPH was evaluated based on variations in the CGI-S and CGAS scales over a 12-month treatment period using linear mixed effects models. A total of 208 ADHD patients and 34 polymorphisms were included in the analysis...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28871186/analysis-of-population-specific-pharmacogenomic-variants-using-next-generation-sequencing-data
#16
Eunyong Ahn, Taesung Park
Functional rare variants in drug-related genes are believed to be highly differentiated between ethnic- or racial populations. However, knowledge of population differentiation (PD) of rare single-nucleotide variants (SNVs), remains widely lacking, with the highest fixation indices, (Fst values), from both rare and common variants annotated to specific genes, having only been marginally used to understand PD at the gene level. In this study, we suggest a new, gene-based PD method, PD of Rare and Common variants (PDRC), for analyzing rare variants, as inspired by Generalized Cochran-Mantel-Haenszel (GCMH) statistics, to identify highly population-differentiated drug response-related genes ("pharmacogenes")...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28868654/impact-of-the-oatp1b1-c-521t-c-single-nucleotide-polymorphism-on-the-pharmacokinetics-of-exemestane-in-healthy-post-menopausal-female-volunteers
#17
B J Gregory, S M Chen, M A Murphy, D H Atchley, L K Kamdem
WHAT IS KNOWN AND OBJECTIVE: OATP1B1 mediates the transport of a diverse range of amphiphilic organic compounds that include bile acids, steroid conjugates and hormones. This retrospective pharmacogenetic study was conducted to assess the impact of the OATP1B1 c.521T>C single nucleotide polymorphism (SNP) on the pharmacokinetics of the steroidal aromatase inhibitor drug exemestane in healthy volunteers. METHODS: Exemestane (25 mg) was administered orally to 14 healthy post-menopausal women...
October 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28867940/genetics-of-generalized-anxiety-disorder-and-related-traits
#18
Michael G Gottschalk, Katharina Domschke
This review serves as a systematic guide to the genetics of generalized anxiety disorder (GAD) and further focuses on anxiety-relevant endophenotypes, such as pathological worry fear of uncertainty, and neuroticism. We inspect clinical genetic evidence for the familialityl heritability of GAD and cross-disorder phenotypes based on family and twin studies. Recent advances of linkage studies, genome-wide association studies, and candidate gene studies (eg, 5-HTT, 5-HT1A, MAOA, BDNF) are outlined. Functional and structural neuroimaging and neurophysiological readouts relating to peripheral stress markers and psychophysiology are further integrated, building a multilevel disease framework...
June 2017: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28862981/need-for-pharmacogenetic-studies-on-the-prevalence-of-mthfr-mutations-in-puerto-ricans-and-hispanics
#19
Raúl H Morales-Borges
Methylenetetrahydrofolate reductase (MTHFR) mutations have been linked to many diseases. Evidence has been provided to prove that we need to perform pharmacogenetic studies regarding the prevalence of MTHFR mutations and diseases, risks, and the impact on folate requirement in general, but little has been published about Puerto Ricans. A multi center cross-sectional retrospective review study or a prospective pharmacogenetic study of valid genotypes and phenotypes of MTHFR mutations within the different populations of Puerto Ricans and Hispanics are recommended, because differences within them and within the general population are expected...
September 1, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28861210/pharmacogenetics-and-precision-medicine-is-inflammation-a-covert-threat-to-effective-genotype-based-therapy
#20
EDITORIAL
Rashmi R Shah
No abstract text is available yet for this article.
September 2017: Therapeutic Advances in Drug Safety
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