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Pharmacogenetics and Genomics

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https://read.qxmd.com/read/30724853/international-survey-of-patients-undergoing-percutaneous-coronary-intervention-and-their-attitudes-toward-pharmacogenetic-testing
#1
Naveen L Pereira, Derek So, Jang-Ho Bae, Ivan Chavez, Myung Ho Jeong, Sang Wook Kim, Mina Madan, John Graham, Fearghas O'Cochlain, Nicole Pauley, Ryan J Lennon, Kent Bailey, Ahmed Hasan, Linnea M Baudhuin, Malcolm R Bell, Amir Lerman, Shaun Goodman, Verghese Mathew, Michael Farkouh, Charanjit S Rihal
OBJECTIVE: To evaluate perceptions toward pharmacogenetic testing of patients undergoing percutaneous coronary intervention (PCI) who are prescribed dual antiplatelet therapy (DAPT) and whether geographical differences in these perceptions exist. PARTICIPANTS AND METHODS: TAILOR-PCI is the largest genotype-based cardiovascular clinical trial randomizing participants to conventional DAPT or prospective genotyping-guided DAPT. Enrolled patients completed surveys before and 6 months after randomization...
February 4, 2019: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30720667/association-of-fam65b-agbl4-and-cux2-genetic-polymorphisms-with-susceptibility-to-antituberculosis-drug-induced-hepatotoxicity-validation-study-in-a-chinese-han-population
#2
Hongqiu Pan, Miaomiao Yang, Lihuan Lu, Bilin Tao, Xiaomin He, Hongbo Chen, Honggang Yi, Shaowen Tang
OBJECTIVE: Antituberculosis (anti-TB) drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction, and its pathogenic mechanism has not been elucidated thoroughly to date. A recent genome-wide association study reported that seven single-nucleotide polymorphisms (SNPs) in the family with sequence similarity 65, member B gene (FAM65B), ATP/GTP-binding protein-like 4 gene (AGBL4), and cut-like homeobox 2 gene (CUX2) were associated strongly with ATDH in Ethiopian patients. We validated this relationship in a Chinese Han anti-TB treatment population...
February 1, 2019: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30694883/associations-between-tmem196-polymorphisms-and-nsaid-exacerbated-respiratory-disease-in-asthma
#3
Jong-Uk Lee, Hun Soo Chang, Dong Gyu Baek, Hyoung Doo Shin, Choon-Sik Park, Jong-Sook Park
BACKGROUND: We previously found differences in the minor allele frequency (MAF) of single-nucleotide polymorphisms (SNPs) in transmembrane protein 196 (TMEM196) between 995 patients with aspirin-tolerant asthma (ATA) and 141 asthmatic patients with NSAID-exacerbated respiratory disease (NERD). In this study, we statistically analyzed the distributions of the genotypes and haplotypes of these SNPs to determine the exact association between TMEM196 genetic variants and the risk for NERD...
January 28, 2019: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30672837/pharmgkb-summary-ondansetron-and-tropisetron-pathways-pharmacokinetics-and-pharmacodynamics
#4
Rachel Huddart, Russ B Altman, Teri E Klein
No abstract text is available yet for this article.
January 21, 2019: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30640894/dna-methylation-is-associated-with-improvement-in-lung-function-on-inhaled-corticosteroids-in-pediatric-asthmatics
#5
Alberta L Wang, Weiliang Qiu, Dawn L DeMeo, Benjamin A Raby, Scott T Weiss, Kelan G Tantisira
Asthma is the most common chronic disease in children. Inhaled corticosteroids (ICS) are the first-line treatment for asthma control, but up to one-third of children have a poor treatment response. The mechanism of ICS resistance is poorly understood, and the role of DNA methylation in ICS treatment response is not known. We examined the association between peripheral blood DNA methylation and ICS treatment response in 152 pediatric persistent asthmatics from the Childhood Asthma Management Program. Response to ICS was measured by the percentage change in forced expiratory volume in 1 s (FEV1) 8 weeks after treatment initiation...
January 11, 2019: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30562214/individuals-with-cyp2c8-and-cyp2c9-reduced-metabolism-haplotypes-self-adjusted-ibuprofen-dose-in-the-coriell-personalized-medicine-collaborative
#6
Stefan C Zajic, Joseph P Jarvis, Pan Zhang, Kaveri D Rajula, Andrew Brangan, Ruth Brenner, Michael P Dempsey, Michael F Christman
OBJECTIVES: The objectives of this study were to determine whether differences in CYP2C8 and CYP2C9 haplotype influence the dose of ibuprofen self-administered by individuals, and to examine the potential relationship between CYP2C8 and CYP2C9 reduced metabolism haplotypes and adverse events. PARTICIPANTS AND METHODS: We investigated relationships between genetic variations in CYP2C8 and CYP2C9 and ibuprofen use, dose, and side effects (reported by questionnaire) in 445 participants from the Coriell Personalized Medicine Collaborative...
December 17, 2018: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30562215/gene-expression-changes-in-lymphoblastoid-cell-lines-and-primary-b-cells-by-dexamethasone
#7
Heung-Woo Park, Amber Dahlin, Weiliang Qiu, Kelan G Tantisira
BACKGROUND: Human Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs) have been thought to be a useful model system for pharmacogenomics studies. The purpose of this study was to determine the effect of Epstein-Barr virus transformation on gene expression changes by dexamethasone (Dex) in LCLs and primary B cells (PBCs) derived from the same individuals. PATIENTS AND METHODS: We prepared LCLs and purified PBCs from the same six male donors participating in the Childhood Asthma Management Program clinical trial, and compared mRNA profiles after 6 h incubation with Dex (10 mol/l) or sham buffer...
December 15, 2018: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30531377/assessment-of-provider-perceived-barriers-to-clinical-use-of-pharmacogenomics-during-participation-in-an-institutional-implementation-study
#8
Brittany A Borden, Paige Galecki, Rebecca Wellmann, Keith Danahey, Sang Mee Lee, Linda Patrick-Miller, Matthew J Sorrentino, Rita Nanda, Jay L Koyner, Tamar S Polonsky, Walter M Stadler, Cathleen Mulcahy, Robert T Kavitt, Mark J Ratain, David O Meltzer, Peter H O'Donnell
OBJECTIVE: The objective of this study was to study provider attitudes of and perceived barriers to the clinical use of pharmacogenomics before and during participation in an implementation program. PARTICIPANTS AND METHODS: From 2012 to 2017, providers were recruited. After completing semistructured interviews (SSIs) about pharmacogenomics, providers received training on and access to a clinical decision support tool housing patient-specific pharmacogenomic results...
December 6, 2018: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30520769/cyp2d6-haplotypes-with-enhancer-single-nucleotide-polymorphism-rs5758550-and-rs16947-2-allele-implications-for-cyp2d6-genotyping-panels
#9
Balmiki Ray, Eren Ozcagli, Wolfgang Sadee, Danxin Wang
INTRODUCTION: CYP2D6 metabolizes ∼25% of all clinically used drugs, with numerous genetic polymorphisms affecting enzyme activity and drug response. Clinical utility of current CYP2D6 genotyping is partially compromised the unresolved complex haplotype structure of the CYP2D6 locus. We have identified a distal enhancer single-nucleotide polymorphism rs5758550 that robustly increases CYP2D6 expression, whereas rs16947 (CYP2D6*2), previously considered inert, reduces correct mRNA splicing and expression, thereby affecting presumed activity of other alleles on the *2 haplotype...
November 28, 2018: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30489455/effect-of-tacrolimus-dispositional-genetics-on-acute-rejection-in-the-first-2-weeks-and-estimated-glomerular-filtration-rate-in-the-first-3-months-following-kidney-transplantation
#10
Rong Hu, Daniel T Barratt, Janet K Coller, Benedetta C Sallustio, Andrew A Somogyi
BACKGROUND: CYP3A4/5 and P-glycoprotein (P-gp, ABCB1) affect tacrolimus (TAC) exposure in T cells and kidney cells. Genetic variability of these genes has been widely studied for effects on acute rejection and kidney function after transplantation, but findings remain contradictory. In addition, cytochrome P450 reductase (POR) is important for CYP3A4/5 activity, and the pregnane X receptor (NR1I2) regulates CYP3A4/5 and P-gp expression. However, the relationship between POR and NR1I2 genetics and acute rejection and kidney function has not been extensively investigated...
November 26, 2018: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30531378/analysis-of-comprehensive-pharmacogenomic-profiling-to-impact-in-hospital-prescribing
#11
Yee Ming Lee, Keith Danahey, Randall W Knoebel, Mark J Ratain, David O Meltzer, Peter H O'Donnell
INTRODUCTION: In-hospital adverse medication events result in increased morbidity and mortality. Many implicated drugs carry pharmacogenomic information. We hypothesized that comprehensive pre-emptive pharmacogenomic profiling could have high relevance for in-hospital prescribing. PATIENTS AND METHODS: We retrospectively analyzed the in-hospital medications of a genotyped outpatient cohort admitted at our institution from 2012 to 2015. The endpoints were medication changes (new medications initiated, dose adjustments, or medications discontinued) involving drugs with pharmacogenomic annotations from three sources: Clinical Pharmacogenetics Implementation Consortium guidance, Food and Drug Administration label information, and drugs with clinical decision supports in our institutional pharmacogenomic Genomic Prescribing System...
February 2019: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30489456/analytical-validity-of-a-genotyping-assay-for-use-with-personalized-antihypertensive-and-chronic-kidney-disease-therapy
#12
Kimberly S Collins, Victoria M Pratt, Wesley M Stansberry, Elizabeth B Medeiros, Karthik Kannegolla, Marelize Swart, Todd C Skaar, Arlene B Chapman, Brian S Decker, Ranjani N Moorthi, Michael T Eadon
Hypertension and chronic kidney disease are inextricably linked. Hypertension is a well-recognized contributor to chronic kidney disease progression and, in turn, renal disease potentiates hypertension. A generalized approach to drug selection and dosage has not proven effective in managing these conditions, in part, because patients with heterogeneous kidney disease and hypertension etiologies are frequently grouped according to functional or severity classifications. Genetic testing may serve as an important tool in the armamentarium of clinicians who embrace precision medicine...
January 2019: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30383576/a-response-letter-to-allopurinol-induced-toxic-epidermal-necrolysis-and-association-with-hla-b-5801-in-white-patients
#13
Dewen Yan, Youming Zhang
No abstract text is available yet for this article.
December 2018: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30383575/alopurinol-induced-ten-and-association-with-hla-b-58-01-in-white-patients
#14
Fabrizzio P Saavedra, Alberto S García, Enrique S González, Luis C L Romero
No abstract text is available yet for this article.
December 2018: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30363031/the-association-between-the-slco1b1-apolipoprotein-e-and-cyp2c9-genes-and-lipid-response-to-fluvastatin-a-meta-analysis
#15
Qian Xiang, Xiaodan Zhang, Lingyue Ma, Kun Hu, Zhuo Zhang, Guangyan Mu, Qiufen Xie, Shuqing Chen, Yimin Cui
OBJECTIVE: The aim of this study was to determine the impact of the SLCO1B1, apolipoprotein E (ApoE), and CYP2C9 genotypes on the lipid-lowering efficacy of fluvastatin. METHODS: We performed electronic searches on the PubMed, Embase, and Cochrane Library databases to identify studies published through October 2017. Studies that reported the effect estimates with 95% confidence intervals (CIs) of total cholesterol (TC), triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein were included so that the different genotype categories could be compared...
December 2018: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30334910/leveraging-electronic-health-records-to-assess-the-role-of-adrb2-single-nucleotide-polymorphisms-in-predicting-exacerbation-frequency-in-asthma-patients
#16
Nikita Sood, John J Connolly, Frank D Mentch, Lyam Vazquez, Patrick M A Sleiman, Erik B Hysinger, Hakon Hakonarson
Asthma is the leading chronic disease in children. Several studies have identified genetic biomarkers associated with susceptibility and severity in both adult and pediatric cases. In this study, we evaluated outcomes in 400 African American and European American pediatric cases all of whom were regular users of inhaled corticosteroids. Patients were stratified by genotype using two single nucleotide polymorphisms in the β-2-adrenergic receptor (ADRB2) gene - rs1042713 and rs1042714, previously associated with asthma outcome...
November 2018: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30334909/pharmacogenetic-variants-and-response-to-neoadjuvant-single-agent-doxorubicin-or-docetaxel-a-study-in-locally-advanced-breast-cancer-patients-participating-in-the-nct00123929-phase-2-randomized-trial
#17
Sara Ruiz-Pinto, Miguel Martin, Guillermo Pita, Daniela Caronia, Julio C de la Torre-Montero, Leticia T Moreno, Fernando Moreno, José Á García-Sáenz, Javier Benítez, Anna González-Neira
OBJECTIVES: Taxanes and anthracyclines are widely used in the treatment of breast cancer, although the benefit is limited to a proportion of patients and predictive biomarkers for clinical outcome remain elusive. PATIENTS AND METHODS: We carried out a pharmacogenetic study in 181 patients with locally advanced breast cancer enrolled in a phase 2 randomized clinical trial (NCT00123929), where patients were randomly assigned to receive neoadjuvant single-agent docetaxel 100 mg/m (n=84) or doxorubicin 75 mg/m (n=97)...
November 2018: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30289819/targeted-sequencing-identifies-a-missense-variant-in-the-best3-gene-associated-with-antihypertensive-response-to-hydrochlorothiazide
#18
Sonal Singh, Zhiying Wang, Mohamed H Shahin, Taimour Y Langaee, Yan Gong, Stephen T Turner, Arlene B Chapman, John G Gums, Caitrin W McDonough, Kent R Bailey, Amber L Beitelshees, Rhonda M Cooper-DeHoff, Steve Scherer, Eric Boerwinkle, Julie A Johnson
Chromosome 12q15 was identified in Genetic Epidemiology of Response Assessment (GERA) and replicated in Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) for its association with blood pressure (BP) response to hydrochlorothiazide (HCTZ). However, the functional variant is unknown and we aimed to identify the likely functional variants through targeted sequencing. The chromosome 12q15 region was sequenced in 397 best and worst responders to HCTZ in PEAR (N=199) and GERA (N=198) hypertensive study participants...
November 2018: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30379713/utility-of-human-leukocyte-antigen-b-58-01-genotyping-and-patient-outcomes
#19
Ching-Hua Ke, Wen-Hung Chung, You-Lin Tain, Yaw-Bin Huang, Yen-Hsia Wen, Hung-Yi Chuang, Chien-Ning Hsu
AIM: Human leukocyte antigen (HLA-B*58:01) allele screening before allopurinol administration is recommended to prevent gene-mediated severe cutaneous adverse reactions (SCARs). The objective of the analysis was to examine the clinical utility and effects of HLA-B*58:01 genotyping on patient's outcomes in a practice setting. PATIENTS AND METHODS: The electronic medical records covering diagnosis, laboratory results, and prescription dispensing for patients who were newly treated with allopurinol or tested for HLA-B*58:01 were obtained from a large medical organization in Taiwan between 2010 and 2014...
October 30, 2018: Pharmacogenetics and Genomics
https://read.qxmd.com/read/30222710/the-role-of-genetic-polymorphisms-in-the-thymidylate-synthase-tyms-gene-in-methotrexate-induced-oral-mucositis-in-children-with-acute-lymphoblastic-leukemia
#20
Natanja Oosterom, Marijn Berrevoets, Marissa A H den Hoed, Oliver Zolk, Susanne Hoerning, Saskia M F Pluijm, Rob Pieters, Robert de Jonge, Wim J E Tissing, Marry M van den Heuvel-Eibrink, Sandra G Heil
OBJECTIVE: Methotrexate (MTX) is an important drug in the treatment of pediatric acute lymphoblastic leukemia (ALL). MTX is cytotoxic as it impairs DNA and RNA synthesis by inhibiting the enzymes dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS). The association between genetic variants within the TYMS gene and MTX-induced toxicity has been studied, but results are inconsistent. We determined the role of three previously described variants within the TYMS gene and MTX-induced oral mucositis in a prospective cohort of Dutch children with ALL and performed a meta-analysis of the previous results...
October 2018: Pharmacogenetics and Genomics
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