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https://www.readbyqxmd.com/read/28073152/characterizing-pharmacogenomic-guided-medication-use-with-a-clinical-data-repository
#1
Patrick C Mathias, Nathaniel Hendrix, Wei-Jhih Wang, Katelyn Keyloun, Maher Khelifi, Peter Tarczy-Hornoch, Beth Devine
The extent to which pharmacogenomic-guided medication use has been adopted in various health systems is unclear. To assess the uptake of pharmacogenomic-guided medication use, we determined its frequency across our health system, which does not have a structured testing program. Using a multi-site clinical data repository, we identified adult patients' first prescribed medications between January 2011 and December 2013 and investigated the frequency of germline and somatic pharmacogenomic testing, by PharmGKB level of FDA label information...
January 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28046094/analysis-of-genetic-variation-in-cyp450-genes-for-clinical-implementation
#2
Liuh Ling Goh, Chia Wei Lim, Wey Cheng Sim, Li Xian Toh, Khai Pang Leong
BACKGROUND: Genetic determinants of drug response remain stable throughout life and offer great promise to patient-tailored drug therapy. The adoption of pharmacogenetic (PGx) testing in patient care requires accurate, cost effective and rapid genotyping with clear guidance on the use of the results. Hence, we evaluated a 32 SNPs panel for implementing PGx testing in clinical laboratories. METHODS: We designed a 32-SNP panel for PGx testing in clinical laboratories...
2017: PloS One
https://www.readbyqxmd.com/read/28002639/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-cyp2d6-genotype-and-use-of-ondansetron-and-tropisetron
#3
Gillian C Bell, Kelly E Caudle, Michelle Whirl-Carrillo, Ronald J Gordon, Keiko Hikino, Cynthia A Prows, Andrea Gaedigk, Jose A G Agundez, Senthilkumar Sadhasivam, Teri E Klein, Matthias Schwab
5-hydroxytryptamine type 3 (5-HT3 ) receptor antagonists are used in the prevention of chemotherapy- induced, radiation-induced and postoperative nausea and vomiting. CYP2D6 polymorphisms can influence the metabolism of some of these drugs (i.e. ondansetron and tropisetron) thereby affecting drug efficacy. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for ondansetron and tropisetron based on CYP2D6 genotype (updates at www.pharmgkb...
December 21, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27992547/the-impact-of-genetic-and-non-genetic-factors-on-warfarin-dose-prediction-in-mena-region-a-systematic-review
#4
Loulia Akram Bader, Hazem Elewa
BACKGROUND: Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing...
2016: PloS One
https://www.readbyqxmd.com/read/27981572/clinical-pharmacogenetics-implementation-consortium-cpic%C3%A2-guideline-for-cyp2c19-and-voriconazole-therapy
#5
Brad Moriyama, Aniwaa Owusu Obeng, Julia Barbarino, Scott R Penzak, Stacey A Henning, Stuart A Scott, José A G Agúndez, John R Wingard, Howard L McLeod, Teri E Klein, Shane Cross, Kelly E Caudle, Thomas J Walsh
Voriconazole, a triazole antifungal agent, demonstrates wide interpatient variability in serum concentrations, due in part to variant CYP2C19 alleles. Individuals who are CYP2C19 ultrarapid metabolizers have decreased trough voriconazole concentrations, delaying achievement of target blood concentrations; whereas, poor metabolizers have increased trough concentrations and are at increased risk of adverse drug events. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of voriconazole for treatment based on CYP2C19 genotype (updates at https://cpicpgx...
December 16, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27864205/evidence-and-resources-to-implement-pharmacogenetic-knowledge-for-precision-medicine
#6
Kelly E Caudle, Roseann S Gammal, Michelle Whirl-Carrillo, James M Hoffman, Mary V Relling, Teri E Klein
PURPOSE: The current state of pharmacogenetic data curation and dissemination is described, and evidence-based resources for applying pharmacogenetic data in clinical practice are reviewed. SUMMARY: Implementation of pharmacogenetics in clinical practice has been relatively slow despite substantial scientific progress in understanding linkages between genetic variation and variability of drug response and effect. One factor that has inhibited the adoption of genetic data to guide medication use is a lack of knowledge of how to translate genetic test results into clinical action based on currently available evidence...
December 1, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27779249/the-global-spectrum-of-protein-coding-pharmacogenomic-diversity
#7
G E B Wright, B Carleton, M R Hayden, C J D Ross
Differences in response to medications have a strong genetic component. By leveraging publically available data, the spectrum of such genomic variation can be investigated extensively. Pharmacogenomic variation was extracted from the 1000 Genomes Project Phase 3 data (2504 individuals, 26 global populations). A total of 12 084 genetic variants were found in 120 pharmacogenes, with the majority (90.0%) classified as rare variants (global minor allele frequency <0.5%), with 52.9% being singletons. Common variation clustered individuals into continental super-populations and 23 pharmacogenes contained highly differentiated variants (FST>0...
October 25, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27750332/-how-to-individualize-drug-therapy-based-on-pharmacogenetic-information-a-systematic-review-of-published-guidelines
#8
Susanne Hafner, Sabine Haubensak, Tanusree Paul, Oliver Zolk
Background | Differences (polymorphisms) in genes encoding drug targets, drug transport proteins, or drug metabolizing enzymes may be responsible, among other factors, for the observed variation in patients' responses to medications. The field of pharmacogenetics aims to identify patients at higher genetically-determined risk of adverse effects or poor response to medication. This information would allow for modification of dosage or substitution with alternative therapy. However, there is a lack of awareness of pharmacogenetic clinical practise guidelines...
October 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27640819/prevalence-and-characteristics-of-adverse-drug-reactions-at-admission-to-hospital-a-prospective-observational-study
#9
Sze Ling Chan, Xiaohui Ang, Levana L Sani, Hong Yen Ng, Michael D Winther, Jian Jun Liu, Liam R Brunham, Alexandre Chan
AIMS: Adverse drug reactions (ADRs) contribute to poorer patient outcomes and additional burden to the healthcare system. However, data on the true burden, relevant types and drugs causing ADRs are lacking. The aim of this study was to determine the prevalence of ADR-related hospitalization in the general adult population in Singapore and to investigate their characteristics. METHODS: We prospectively recruited 1000 adult patients with unplanned admission to a large tertiary-care hospital...
December 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27636560/pharmgkb-summary-ivacaftor-pathway-pharmacokinetics-pharmacodynamics
#10
Alison E Fohner, Ellen M McDonagh, John P Clancy, Michelle Whirl Carrillo, Russ B Altman, Teri E Klein
No abstract text is available yet for this article.
January 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/27414743/genetic-polymorphisms-study-of-pharmacogenomic-vip-variants-in-han-ethnic-of-china-s-shaanxi-province
#11
Tianbo Jin, Ruimin Zhao, Xugang Shi, Na He, Xue He, Yongri Ouyang, Hong Wang, Bo Wang, Longli Kang, Dongya Yuan
BACKGROUND: Multiple factors include genetic and non-genetic interactions induce to different drug response among different individuals. Lots of researches proved that different frequencies of genetic variants exists different ethnic groups. The aim of this study was to screen Han volunteers in Shaanxi for VIP gene polymorphisms. MATERIALS AND METHODS: We genotyped 80 Very Important Pharmacogenes (VIP) (selected from the PharmGKB database) in 192 unrelated, healthy Han ethnic adults from Shaanxi, the northwest of China, and then analyzed genotyping data wtih Structure and F-statistics (Fst) analysis...
September 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/27253732/pharmacogenomic-incidental-findings-in-308-families-the-nih-undiagnosed-diseases-program-experience
#12
Elizabeth M J Lee, Karen Xu, Emma Mosbrook, Amanda Links, Jessica Guzman, David R Adams, Elise Flynn, Elise Valkanas, Camillo Toro, Cynthia J Tifft, Cornelius F Boerkoel, William A Gahl, Murat Sincan
PURPOSE: Using single-nucleotide polymorphism (SNP) chip and exome sequence data from individuals participating in the National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP), we evaluated the number and therapeutic informativeness of incidental pharmacogenetic variants. METHODS: Pharmacogenomics Knowledgebase (PharmGKB) annotated sequence variants were identified in 1,101 individuals. Medication records of participants were used to identify individuals prescribed medications with a genetic variant that might alter efficacy...
December 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27233804/genetic-polymorphisms-of-pharmacogenomic-vip-variants-in-the-mongol-of-northwestern-china
#13
Tianbo Jin, Xugang Shi, Li Wang, Huijuan Wang, Tian Feng, Longli Kang
BACKGROUND: Within a population, the differences of pharmacogenomic variant frequencies may produce diversities in drug efficacy, safety, and the risk associated with adverse drug reactions. With the development of pharmacogenomics, widespread genetic research on drug metabolism has been conducted on major populations, but less is known about minorities. RESULTS: In this study, we recruited 100 unrelated, healthy Mongol adults from Xinjiang and genotyped 85 VIP variants from the PharmGKB database...
2016: BMC Genetics
https://www.readbyqxmd.com/read/27232112/pharmgkb-summary-isoniazid-pathway-pharmacokinetics
#14
Daniel J Klein, Sotiria Boukouvala, Ellen M McDonagh, Scott R Shuldiner, Nicola Laurieri, Caroline F Thorn, Russ B Altman, Teri E Klein
No abstract text is available yet for this article.
September 2016: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/26901752/genetic-polymorphisms-of-pharmacogenomic-vip-variants-in-li-nationality-of-southern-china
#15
Yipeng Ding, Ping He, Na He, Quanni Li, Juan Sun, Jinjian Yao, Shengyang Yi, Heping Xu, Duoyi Wu, Xiang Wang, Tianbo Jin
OBJECTIVES: The present study aimed to screen members of the Li nationality in southern China for genotype frequencies of VIP variants and to determine differences between the Li ethnicity and global human population samples in HapMap. METHODS: In this study, we genotyped 77 very important pharmacogenetic (VIP) variants selected from the pharmacogenomics knowledge base (PharmGKB) in members of the Li population and compared our data with other eleven populations from the HapMap data set...
March 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/26900164/featured-article-genotation-actionable-knowledge-for-the-scientific-reader
#16
Panduka Nagahawatte, Ethan Willis, Mark Sakauye, Rony Jose, Hao Chen, Robert L Davis
We present an article viewer application that allows a scientific reader to easily discover and share knowledge by linking genomics-related concepts to knowledge of disparate biomedical databases. High-throughput data streams generated by technical advancements have contributed to scientific knowledge discovery at an unprecedented rate. Biomedical Informaticists have created a diverse set of databases to store and retrieve the discovered knowledge. The diversity and abundance of such resources present biomedical researchers a challenge with knowledge discovery...
June 2016: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/26801900/pharmacogenetics-driving-personalized-medicine-analysis-of-genetic-polymorphisms-related-to-breast-cancer-medications-in-italian-isolated-populations
#17
Massimiliano Cocca, Davide Bedognetti, Martina La Bianca, Paolo Gasparini, Giorgia Girotto
BACKGROUND: Breast cancer is the most common cancer in women characterized by a high variable clinical outcome among individuals treated with equivalent regimens and novel targeted therapies. In this study, we performed a population based approach intersecting high-throughput genotype data from Friuli Venezia Giulia (FVG) isolated populations with publically available pharmacogenomics information to estimate the frequency of genotypes correlated with responsiveness to breast cancer treatment thus improving the clinical management of this disease in an efficient and cost effective way...
January 22, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/26709912/pharmgkb-summary-very-important-pharmacogene-information-for-ryr1
#18
REVIEW
Maria L Alvarellos, Ronald M Krauss, Russell A Wilke, Russ B Altman, Teri E Klein
No abstract text is available yet for this article.
March 2016: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/26632549/genetic-polymorphisms-analysis-of-pharmacogenomic-vip-variants-in-miao-ethnic-group-of-southwest-china
#19
Tianbo Jin, Ainiwaer Aikemu, Mingxi Zhang, Tingting Geng, Tian Feng, Longli Kang, Man Lin Luo
BACKGROUND Genetic polymorphisms have a potential clinical role in determining both inter-individual and inter-ethnic differences in drug efficacy, but we have not found any pharmacogenomics information regarding minorities, such as the Miao ethnic group. Our study aimed to screen numbers of the Miao ethnic group for genotype frequencies of VIP variants and to determine differences between the Miao and other human populations worldwide. MATERIAL AND METHODS In this study, we genotyped 66 Very Important Pharmacogene (VIP) variants selected from PharmGKB in 98 unrelated, healthy Miao individuals from the Guizhou province and compared our data with 12 other populations, including 11 populations from the HapMap data set and Xi'an Han Chinese...
December 3, 2015: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/26417955/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-ugt1a1-and-atazanavir-prescribing
#20
REVIEW
R S Gammal, M H Court, C E Haidar, O F Iwuchukwu, A H Gaur, M Alvarellos, C Guillemette, J L Lennox, M Whirl-Carrillo, S S Brummel, M J Ratain, T E Klein, B R Schackman, K E Caudle, D W Haas
The antiretroviral protease inhibitor atazanavir inhibits hepatic uridine diphosphate glucuronosyltransferase (UGT) 1A1, thereby preventing the glucuronidation and elimination of bilirubin. Resultant indirect hyperbilirubinemia with jaundice can cause premature discontinuation of atazanavir. Risk for bilirubin-related discontinuation is highest among individuals who carry two UGT1A1 decreased function alleles (UGT1A1*28 or *37). We summarize published literature that supports this association and provide recommendations for atazanavir prescribing when UGT1A1 genotype is known (updates at www...
April 2016: Clinical Pharmacology and Therapeutics
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