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https://www.readbyqxmd.com/read/28871186/analysis-of-population-specific-pharmacogenomic-variants-using-next-generation-sequencing-data
#1
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/28858993/pharmgkb-summary-very-important-pharmacogene-information-for-abcg2
#2
Alison E Fohner, Deanna J Brackman, Kathleen M Giacomini, Russ B Altman, Teri E Klein
No abstract text is available yet for this article.
August 29, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28678138/pharmgkb-summary-pazopanib-pathway-pharmacokinetics
#3
Caroline F Thorn, Manish R Sharma, Russ B Altman, Teri E Klein
No abstract text is available yet for this article.
August 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28654193/serotonin-transporter-gene-polymorphisms-and-selective-serotonin-reuptake-inhibitor-tolerability-review-of-pharmacogenetic-evidence
#4
REVIEW
Jing Zhu, Michele Klein-Fedyshin, James M Stevenson
Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacotherapy for mood and anxiety disorders. The common mechanism of drugs in this class is antagonism of the serotonin transporter. Within the serotonin transporter gene SLC6A4, two polymorphic sites termed 5-HTTLPR and STin2 are proposed to have functional consequences and thus have been attractive candidates for pharmacogenetic studies of SSRI efficacy and tolerability. This review summarizes approximately 15 years of study of these polymorphisms as they relate to SSRI tolerability phenotypes...
September 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28629370/pharmacogenetic-testing-through-the-direct-to-consumer-genetic-testing-company-23andme
#5
Mengfei Lu, Cathryn M Lewis, Matthew Traylor
BACKGROUND: Rapid advances in scientific research have led to an increase in public awareness of genetic testing and pharmacogenetics. Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals. Here, we evaluate the clinical relevance of pharmacogenetic tests reported by 23andMe in their UK tests. METHODS: The research papers listed under each 23andMe report were evaluated, extracting information on effect size, sample size and ethnicity...
June 19, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28452122/identification-of-sequence-variants-within-experimentally-validated-protein-interaction-sites-provides-new-insights-into-molecular-mechanisms-of-disease-development
#6
Blaz Skrlj, Janez Konc, Tanja Kunej
Protein interactions (PI) underlie complex biological processes. Protein interaction partners include DNA, RNA, ions, small chemical compounds, and proteins (protein-protein interactions; PPI). Analysis of sequence variants within regions corresponding to experimentally validated PI sites presents novel opportunities for understanding of complex diseases. Such information has not been systematically collected due to the fact that datasets are dispersed throughout databases and publications. Sequence variants and PI regions were obtained from the UniProt database...
April 28, 2017: Molecular Informatics
https://www.readbyqxmd.com/read/28362716/pharmgkb-summary-sorafenib-pathways
#7
Li Gong, Marilyn M Giacomini, Craig Giacomini, Michael L Maitland, Russ B Altman, Teri E Klein
No abstract text is available yet for this article.
June 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28339805/design-and-evaluation-of-a-pharmacogenomics-information-resource-for-pharmacists
#8
Katrina M Romagnoli, Richard D Boyce, Philip E Empey, Yifan Ning, Solomon Adams, Harry Hochheiser
Objective: To develop and evaluate a pharmacogenomics information resource for pharmacists. Materials and Methods: We built a pharmacogenomics information resource presenting Food and Drug Administration (FDA) drug product labelling information, refined it based on feedback from pharmacists, and conducted a comparative usability evaluation, measuring task completion time, task correctness and perceived usability. Tasks involved hypothetical clinical situations requiring interpretation of pharmacogenomics information to determine optimal prescribing for specific patients...
February 26, 2017: Journal of the American Medical Informatics Association: JAMIA
https://www.readbyqxmd.com/read/28315856/an-update-on-hla-alleles-associated-with-adverse-drug-reactions
#9
REVIEW
Ingrid Fricke-Galindo, Adrián LLerena, Marisol López-López
Adverse drug reactions (ADRs) are considered as an important cause of morbidity and mortality. The hypersensitivity reactions are immune-mediated ADRs, which are dose-independent, unpredictable and have been associated with several HLA alleles. The present review aimed to describe HLA alleles that have been associated with different ADRs in populations worldwide, the recommendations of regulatory agencies and pharmacoeconomic information and databases for the study of HLA alleles in pharmacogenetics. A systematic search was performed in June 2016 of articles relevant to this issue in indexed journals and in scientific databases (PubMed and PharmGKB)...
May 24, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28277330/pharmgkb-summary-voriconazole-pathway-pharmacokinetics
#10
Julia M Barbarino, Aniwaa Owusu Obeng, Teri E Klein, Russ B Altman
No abstract text is available yet for this article.
May 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28146011/pharmgkb-summary-macrolide-antibiotic-pathway-pharmacokinetics-pharmacodynamics
#11
Alison E Fohner, Alex Sparreboom, Russ B Altman, Teri E Klein
No abstract text is available yet for this article.
April 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28099408/multiphenotype-association-study-of-patients-randomized-to-initiate-antiretroviral-regimens-in-aids-clinical-trials-group-protocol-a5202
#12
Anurag Verma, Yuki Bradford, Shefali S Verma, Sarah A Pendergrass, Eric S Daar, Charles Venuto, Gene D Morse, Marylyn D Ritchie, David W Haas
BACKGROUND: High-throughput approaches are increasingly being used to identify genetic associations across multiple phenotypes simultaneously. Here, we describe a pilot analysis that considered multiple on-treatment laboratory phenotypes from antiretroviral therapy-naive patients who were randomized to initiate antiretroviral regimens in a prospective clinical trial, AIDS Clinical Trials Group protocol A5202. PARTICIPANTS AND METHODS: From among 5 9545 294 polymorphisms imputed genome-wide, we analyzed 2544, including 2124 annotated in the PharmGKB, and 420 previously associated with traits in the GWAS Catalog...
March 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28073152/characterizing-pharmacogenomic-guided-medication-use-with-a-clinical-data-repository
#13
MULTICENTER STUDY
P C Mathias, N Hendrix, W-J Wang, K Keyloun, M Khelifi, P Tarczy-Hornoch, B 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 multisite 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 the Pharmacogenomics Knowledgebase level of the US Food and Drug Administration label information...
August 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28046094/analysis-of-genetic-variation-in-cyp450-genes-for-clinical-implementation
#14
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
#15
G C Bell, K E Caudle, M Whirl-Carrillo, R J Gordon, K Hikino, C A Prows, A Gaedigk, Jag Agundez, S Sadhasivam, T E Klein, M Schwab
No abstract text is available yet for this article.
August 2017: 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
#16
REVIEW
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-guidelines-for-cyp2c19-and-voriconazole-therapy
#17
B Moriyama, A Owusu Obeng, J Barbarino, S R Penzak, S A Henning, S A Scott, Jag Agúndez, J R Wingard, H L McLeod, T E Klein, S J Cross, K E Caudle, T 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
#18
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
#19
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
#20
REVIEW
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
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