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Pharmacogenomics

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https://www.readbyqxmd.com/read/29095114/triple-negative-breast-cancer-and-the-potential-for-targeted-therapy
#1
Jing-Ru Jhan, Eran R Andrechek
Breast cancer is composed of several well-recognized subtypes including estrogen receptor, progesterone receptor and HER2 triple-negative breast cancer (TNBC). Without available targeted therapy options, standard of care for TNBC remains chemotherapy. It is of interest to note that TNBC tumors generally have better responses to chemotherapy compared with other subtypes. However, patients without complete response account for approximately 80% of TNBC. Mounting evidence suggests significant heterogeneity within the TNBC subtype, and studies have focused on genetic targets with high rates of altered expression...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29095108/pharmacogenetics-of-glatiramer-acetate-therapy-for-multiple-sclerosis-the-impact-of-genome-wide-association-studies-identified-disease-risk-loci
#2
Olga Kulakova, Vitalina Bashinskaya, Ivan Kiselev, Natalia Baulina, Ekaterina Tsareva, Ruslan Nikolaev, Maxim Kozin, Sergey Shchur, Alexander Favorov, Alexey Boyko, Olga Favorova
AIM: Association analysis of genome-wide association studies (GWAS) identified multiple sclerosis (MS) risk genetic variants with glatiramer acetate (GA) treatment efficacy. PATIENTS & METHODS: SNPs in 17 GWAS-identified immune response loci were analyzed in 296 Russian MS patients as possible markers of optimal GA treatment response for at least 2 years. RESULTS: Alleles/genotypes of EOMES, CLEC16A, IL22RA2, PVT1 and HLA-DRB1 were associated by themselves with event-free phenotype during GA treatment for at least 2 years (p f  = 0...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29095107/slco1b1-rs4149056-genetic-polymorphism-predicting-methotrexate-toxicity-in-chinese-patients-with-non-hodgkin-lymphoma
#3
Lin Yang, Hui Wu, Teun van Gelder, Maja Matic, Jun-Shan Ruan, Yong Han, Rui-Xiang Xie
AIM: To investigate the impact of polymorphisms in the FPGS, GGH and SLCO1B1 genes on high dose methotrexate (HD-MTX) related toxicity in Chinese patients with non-Hodgkin lymphoma (NHL). MATERIALS & METHODS: We analyzed FPGS (rs10106), GGH (rs719235, rs10464903, rs12681874), SLCO1B1 (rs4149056) genetic polymorphisms in 105 Chinese patients with NHL treated with HD-MTX. RESULTS: There was a statistically significant impact of the SLCO1B1 rs4149056 polymorphism on hepatotoxicity...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29095105/genotype-based-tacrolimus-dosing-guidelines-with-or-without-cyp3a4-22
#4
Laure Elens, Vincent Haufroid
AIM: To test the relevance of revisiting the genotype classification based on CYP3A5*3 solely by incorporating CYP3A4*22 information. METHODS: Discriminant analysis of principal component was performed to evaluate the relevance of either the CYP3A (CYP3A5 + CYP3A4 genotypes) or CYP3A5*3 classification variables. This analysis was based on a linear combination of noncompartmental pharmacokinetics parameters. RESULTS: Discriminant analysis of principal component gave better results with CYP3A compared with CYP3A5*3 clustering...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29095103/distinctiveness-of-the-roma-population-within-cyp2b6-worldwide-variation
#5
Željka Tomas, Antonija Kuhanec, Tatjana Škarić-Jurić, Matea Zajc Petranović, Nina Smolej Narančić, Branka Janićijević, Marijana Peričić Salihović
AIM: To determine variation of CYP2B6 gene within the genetically specific Croatian Roma (Gypsy) population originating from India and to examine it in the worldwide perspective. MATERIALS & METHODS: Seven SNP loci (rs12721655, rs2279343, rs28399499, rs34097093, rs3745274, rs7260329 and rs8192709) were genotyped in 439 subjects using Kompetitive Allele Specific PCR (KASP) method. RESULTS: The Croatian Roma took an outlying position in CYP2B6 variation from the worldwide perspective mainly due to their exceptionally high minor allele frequency (MAF) for rs8192709 (12...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29095100/rethinking-ovarian-cancer-genomics-where-genome-wide-association-studies-stand
#6
Ricardo Pinto, Joana Assis, Augusto Nogueira, Carina Pereira, Deolinda Pereira, Rui Medeiros
Genome-wide association studies (GWAS) allow the finding of genetic variants associated with several traits. Regarding ovarian cancer (OC), 15 GWAS have been conducted since 2009, with the discovery of 49 SNPs associated with disease susceptibility and 46 with impact in the clinical outcome of patients (p < 5.00 × 10(-2)). Among them, 14 variants reached the genome-wide significance (p < 5.00 × 10(-8)). Despite the results obtained, they should be validated in independent sets. So far, five validation studies have been conducted which could confirm the association of 12 OC susceptibility SNPs...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29095091/an-assessment-of-the-impact-of-pharmacogenomics-on-health-disparities-a-systematic-literature-review
#7
Antony Martin, Jennifer Downing, Michelle Maden, Nigel Fleeman, Ana Alfirevic, Alan Haycox, Munir Pirmohamed
This review assessed evidence of disparities in benefits of pharmacogenomics related to 'model performance' in subgroups of patients and studies which reported impact on health inequalities. 'Model performance' refers to the ability of algorithms including clinical, environmental and genetic information to guide treatment. A total of 4978 abstracts were screened by one reviewer and 30% (1494) were double screened by a second independent reviewer, after which data extraction was performed. Additional forward and backward citation searching of reference lists was conducted...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29095089/impact-of-cyp2d6-and-adrb1-polymorphisms-on-heart-rate-of-post-pci-patients-treated-with-metoprolol
#8
Xiaofeng Gao, Huan Wang, Hui Chen
AIM: To explore the effect of CYP2D6*10 (100C > T) and ADRB1 1165 G > C polymorphisms on heart rate of post-PCI (percutaneous coronary intervention) patients treated with metoprolol succinate sustained-release tablets. METHODS: A total of 756 inpatients with metoprolol succinate sustained-release tablets were selected and the genotypes of CYP2D6*10 and ADRB1 1165G > C were detected in 319 patients using gene chip detection. The target heart rate was defined as a resting heart rate < 70 beats/min...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29061087/oct1-pharmacogenetics-in-pain-management-is-a-clinical-application-within-reach
#9
Mladen V Tzvetkov
Beside drug metabolizing enzymes alsogenetically variable membrane transporters may substantially contribute to the interindividual variability in pharmacokinetics and efficacy of opioids and other analgesics. The organic cation transporter OCT1 is strongly expressed in the sinusoidal membrane of the human liver. It may affect hepatic uptake and thus limit metabolic rates. OCT1 is highly genetically variable. Genetic polymorphisms lead to substantially reduced OCT1 activity in up to 9% of the Europeans and the white Americans...
October 24, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29061086/pharmacogenetics-based-population-pharmacokinetic-analysis-of-tenofovir-in-thai-hiv-infected-patients
#10
Kanokrat Rungtivasuwan, Anchalee Avihingsanon, Narukjaporn Thammajaruk, Siwaporn Mitruk, David M Burger, Kiat Ruxrungtham, Chonlaphat Sukasem, Baralee Punyawudho
AIM: To develop a population pharmacokinetic model and identify sources of variability, genetic and nongenetic factors, of tenofovir. METHODS: The ABCC2 and ABCC4 polymorphisms were genotyped in 342 patients. A nonlinear mixed effects model was used to develop the population pharmacokinetic model and investigate the influence of these polymorphisms and other patient specific covariates on the pharmacokinetics of tenofovir. RESULTS: The estimated glomerular filtration rate calculated by the Cockcroft and Gault equation, concomitant use of lopinavir/ritonavir and ABCC4 3463A>G polymorphism were associated with tenofovir apparent oral clearance (CL/F)...
October 24, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29061085/do-genes-affect-morphine-response
#11
Louise Ladebo, Anne Estrup Olesen
No abstract text is available yet for this article.
October 24, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29061081/pharmacogenetics-of-trazodone-in-healthy-volunteers-association-with-pharmacokinetics-pharmacodynamics-and-safety
#12
Miriam Saiz-Rodríguez, Carmen Belmonte, Nieves Derqui-Fernández, Teresa Cabaleiro, Manuel Román, Dolores Ochoa, María Talegón, María C Ovejero-Benito, Francisco Abad-Santos
AIM: The aim was to evaluate the effect of polymorphisms in metabolizing enzymes and transporters on the pharmacokinetics, pharmacodynamics and adverse effects of trazodone in healthy volunteers. MATERIALS & METHODS: 36 healthy volunteers receiving a single 100-mg oral dose of trazodone were genotyped for 11 variants in CYP3A4, CYP3A5, CYP2D6 and ABCB1 by real-time PCR. Plasma concentrations were measured using liquid chromatography-tandem mass spectrometry method...
October 24, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29061079/precision-oncology-neither-a-silver-bullet-nor-a-dream
#13
Nora S Sánchez, Gordon B Mills, Kenna R Mills Shaw
Precision oncology is not an illusion, nor is it the magic bullet that will eradicate all cancers. Precision oncology is simply another weapon in our growing armament against cancer. Rather than honing in on the failures of a relatively young field, one should advocate for integrating its successes into widespread clinical practice, especially for indications, such as: ABL, ALK, BRAF, BRCA1, BRCA2, EGFR, KIT, KRAS, PDGFRA, PDGFRB, ROS1, BCR-ABL, FLT3 and ROS1, where aberrations have been shown to alter responses to US FDA approved drugs - that is, level 1 data...
October 24, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29061078/introducing-personalized-health-for-the-family-the-experience-of-a-single-hospital-system
#14
Kathi L Huddleston, Elisabeth Klein, Alma Fuller, Grace Jo, Grace Lawrence, Susanne B Haga
Pharmacogenetic testing is leading the personalized health movement, gradually being implemented in a variety of healthcare settings. To inform the efforts of other hospital and clinical practices implementing personalized health or medicine applications, we describe the implementation of a newborn pharmacogenetic testing program at Inova Health System (VA, USA). In particular, we describe the efforts to gather patient feedback through focus groups, the training and program staff, the pilot program and our experiences to date...
October 24, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29057710/integrative-cancer-pharmacogenomics-to-establish-drug-mechanism-of-action-drug-repurposing
#15
Nehme El-Hachem, Wail Ba-Alawi, Ian Smith, Arvind Singh Mer, Benjamin Haibe-Kains
No abstract text is available yet for this article.
October 23, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29053440/association-of-the-hla-b-alleles-with-carbamazepine-induced-stevens-johnson-syndrome-toxic-epidermal-necrolysis-in-the-javanese-and-sundanese-population-of-indonesia-the-important-role-of-the-hla-b75-serotype
#16
Rika Yuliwulandari, Erna Kristin, Kinasih Prayuni, Qomariyah Sachrowardi, Franciscus D Suyatna, Sri Linuwih Menaldi, Nuanjun Wichukchinda, Surakameth Mahasirimongkol, Larisa H Cavallari
Carbamazepine (CBZ) is a common cause of life-threatening cutaneous adverse drug reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Previous studies have reported a strong association between the HLA genotype and CBZ-induced SJS/TEN. We investigated the association between the HLA genotype and CBZ-induced SJS/TEN in Javanese and Sundanese patients in Indonesia. Nine unrelated patients with CBZ-induced SJS/TEN and 236 healthy Javanese and Sundanese controls were genotyped for HLA-B and their allele frequencies were compared...
October 20, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29020843/interview-about-the-gift-trial-pharmacogenetics-and-warfarin
#17
Brian F Gage
No abstract text is available yet for this article.
October 12, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29017379/hla-associated-drug-hypersensitivity-and-the-prediction-of-adverse-drug-reactions
#18
Simone Negrini, Laurent Becquemont
Adverse drug reactions are an important cause of morbidity and mortality and constitute the leading reason of drug withdrawal from the market. Besides classical reactions that are related to pharmacologic activity of the drug, some reactions are unpredictable, not dose dependent, and seem to occur in genetically predisposed individuals. The majority of this reaction is immunologically driven and they are referred to as hypersensitivity reactions. A growing number of studies provided evidences that specific HLA alleles increase the risk of developing hypersensitivity drug reactions...
October 11, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28982277/corrigendum
#19
(no author information available yet)
No abstract text is available yet for this article.
October 6, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28982267/institutional-profile-translational-pharmacogenomics-at-the-icahn-school-of-medicine-at-mount-sinai
#20
Stuart A Scott, Aniwaa Owusu Obeng, Mariana R Botton, Yao Yang, Erick R Scott, Stephen B Ellis, Richard Wallsten, Tom Kaszemacher, Xiang Zhou, Rong Chen, Paola Nicoletti, Hetanshi Naik, Eimear E Kenny, Aida Vega, Eva Waite, George A Diaz, Joel Dudley, Jonathan L Halperin, Lisa Edelmann, Andrew Kasarskis, Jean-Sébastien Hulot, Inga Peter, Erwin P Bottinger, Kurt Hirschhorn, Pamela Sklar, Judy H Cho, Robert J Desnick, Eric E Schadt
For almost 50 years, the Icahn School of Medicine at Mount Sinai has continually invested in genetics and genomics, facilitating a healthy ecosystem that provides widespread support for the ongoing programs in translational pharmacogenomics. These programs can be broadly cataloged into discovery, education, clinical implementation and testing, which are collaboratively accomplished by multiple departments, institutes, laboratories, companies and colleagues. Focus areas have included drug response association studies and allele discovery, multiethnic pharmacogenomics, personalized genotyping and survey-based education programs, pre-emptive clinical testing implementation and novel assay development...
October 6, 2017: Pharmacogenomics
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