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Pharmacogenomics Journal

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https://www.readbyqxmd.com/read/30405212/tenofovir-disoproxil-fumarate-discontinuation-for-renal-outcomes-any-room-for-treatment-personalization
#1
A Calcagno, M Fiumanò, D Zugna, J Cusato, C Montrucchio, L Marinaro, L Trentini, M Ferrara, A D'Avolio, C Pizzi, G Di Perri, S Bonora
Tenofovir disoproxil fumarate (TDF) is a very effective antiviral drug that has been associated with tubular dysfunction. The aim of this study was to analyze the demographic, pharmacokinetic, and pharmacogenetic variables associated with TDF discontinuation for renal outcomes in stable HIV-positive patients using multivariable analyses. Three hundred and four patients were included (73% male, with median age and eCrCl of 45.3 years and 90.9 mL/min, respectively). After a median follow-up of 28.3 months, 27 patients discontinued TDF for renal adverse events [persistent urinary abnormalities (n = 21) or eCrCl < 60 mL/min (n = 6)] providing an incidence of 3...
November 8, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30393374/iatrogenic-hypertension-a-bioinformatic-analysis
#2
Alon Botzer, Yoram Finkelstein, Ehud Grossman, John Moult, Ron Unger
It is well known that a myriad of medications and substances can induce side effects that are related to blood pressure (BP) regulation. This study aims to investigate why certain drugs tend to cause iatrogenic hypertension (HTN) and focus on drug targets that are implicated in these conditions.Databases and resources such as SIDER, DrugBank, and Genomatix were utilized in order to bioinformatically investigate HTN-associated drug target-genes for which HTN is a side effect. A tree-like map was created, representing interactions between 198 human genes that relate to the blood pressure system...
November 5, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30368523/replication-of-the-pharmacogenetic-effect-of-rs678849-on-buprenorphine-efficacy-in-african-americans-with-opioid-use-disorder
#3
Richard C Crist, Karran A Phillips, Melody A Furnari, Landhing M Moran, Glenn A Doyle, Laura F McNicholas, James W Cornish, Kyle M Kampman, Kenzie L Preston, Wade H Berrettini
Many patients with opioid use disorder do not have successful outcomes during treatment but the underlying reasons are not well understood. An OPRD1 variant (rs678849) was previously associated with methadone and buprenorphine efficacy in African-Americans with opioid use disorder. The objective of this study was to determine if the effect of rs678849 on opioid use disorder treatment outcome could be replicated in an independent population. Participants were recruited from African-American patients who had participated in previous studies of methadone or buprenorphine treatment at the outpatient treatment research clinic of the NIDA Intramural Research Program in Baltimore, MD, USA between 2000 and 2017...
October 27, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30323313/impact-of-single-nucleotide-polymorphisms-on-p450-oxidoreductase-and-peroxisome-proliferator-activated-receptor-alpha-on-tacrolimus-pharmacokinetics-in-renal-transplant-recipients
#4
Shuhui Si, Zijie Wang, Haiwei Yang, Zhijian Han, Jun Tao, Hao Chen, Ke Wang, Miao Guo, Ruoyun Tan, Ji-Fu Wei, Min Gu
The P450 oxidoreductase (POR) and peroxisome proliferator-activated receptor alpha (PPARA) genes are associated with the activity of cytochrome P450 enzymes in vivo. We aimed to investigate the impact of single nucleotide polymorphisms (SNPs) in the POR and PPARA genes on the pharmacokinetics of tacrolimus (TAC) in renal transplant recipients. A total of 220 recipients were assessed and 105 recipients were included for final quantitative analysis. Blood samples were collected and DNA was extracted. Targeting sequencing based on next-generation sequencing was applied to detect the SNPs in the POR and PPARA genes...
October 15, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30293984/long-range-pcr-libraries-and-next-generation-sequencing-for-pharmacogenetic-studies-of-patients-treated-with-anti-tnf-drugs
#5
Michal Walczak, Marzena Skrzypczak-Zielinska, Marianna Plucinska, Oliwia Zakerska-Banaszak, Daria Marszalek, Liliana Lykowska-Szuber, Kamila Stawczyk-Eder, Agnieszka Dobrowolska, Ryszard Slomski
Biological therapy with anti-tumor necrosis factor-α (anti-TNF-α) monoclonal antibodies significantly increased the effectiveness of autoimmune disease treatment compared with conventional medicines. However, anti-TNF-α drugs are relatively expensive and a response to the therapy is reported in only 60-70% of patients. Moreover, in up to 5% of patients adverse drug reactions occur. The various effects of biological treatment may be a potential consequence of interindividual genetic variability. Only a few studies have been conducted in this field and which refer to single gene loci...
October 8, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30287911/association-between-sost-gene-polymorphisms-and-response-to-alendronate-treatment-in-postmenopausal-chinese-women-with-low-bone-mineral-density
#6
REVIEW
W-J Wang, W-Z Fu, J-W He, C Wang, Z-L Zhang
The aim of this study was to explore the allelic association between SOST polymorphisms and the variance of clinical effects of alendronate in postmenopausal Chinese women with osteoporosis or osteopenia. In the study, 500 postmenopausal women in Shanghai area with osteoporosis or osteopenia were included. All participants were treated with weekly oral alendronate 70 mg, daily calcium 600 mg and vitamin D 125 IU for 12 months. Nine tagging single-nucleotide polymorphisms (SNPs) in SOST gene were genotyped...
October 5, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30287910/pharmacogenomics-in-epithelial-ovarian-cancer-first-line-treatment-outcome-validation-of-gwas-associated-nrg3-rs1649942-and-bre-rs7572644-variants-in-an-independent-cohort
#7
Ricardo Pinto, Joana Assis, Augusto Nogueira, Carina Pereira, Sara Coelho, Mariana Brandão, João Dias, Sara Alves, Deolinda Pereira, Rui Medeiros
The identification of predictive biomarkers for the first-line treatment of epithelial ovarian cancer (EOC) remains a challenge. Although genome-wide association studies (GWAS) have identified several genetic polymorphisms as predictors of EOC clinical outcome, the subsequent validation has not yet been performed. This study aims to validate the influence of Neuregulin 3 (NRG3) rs1649942 and Brain and reproductive organ-expressed (TNFRSF1A modulator) (BRE) rs7572644 GWAS-identified variants in an independent cohort of EOC patients from the North region of Portugal (n = 339) submitted to first-line treatment...
October 5, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30287909/polymorphisms-at-phase-i-metabolizing-enzyme-and-hormone-receptor-loci-influence-the-response-to-anti-tnf-therapy-in-rheumatoid-arthritis-patients
#8
Luz M Canet, Jose M Sánchez-Maldonado, Rafael Cáliz, Ana Rodríguez Ramos, Carmen B Lupiañez, Helena Canhão, Manuel Martínez-Bueno, Alejandro Escudero, Juana Segura-Catena, Signe B Sorensen, Merete L Hetland, María José Soto-Pino, Miguel A Ferrer, Antonio García, Bente Glintborg, Ileana Filipescu, Eva Pérez-Pampin, Alfonso González-Utrilla, Miguel Ángel López Nevot, Pablo Conesa-Zamora, Alfons den Broeder, Salvatore De Vita, Sven Erik Hobe Jacobsen, Eduardo Collantes-Estevez, Luca Quartuccio, Federico Canzian, João E Fonseca, Marieke J H Coenen, Vibeke Andersen, Juan Sainz
The aim of this case-control study was to evaluate whether 47 single-nucleotide polymorphisms (SNPs) in steroid hormone-related genes are associated with the risk of RA and anti-TNF drug response. We conducted a case-control study in 3 European populations including 2936 RA patients and 2197 healthy controls. Of those, a total of 1985 RA patients were treated with anti-TNF blockers. The association of potentially interesting markers in the discovery population was validated through meta-analysis with data from DREAM and DANBIO registries...
October 5, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30262821/genome-wide-enrichment-of-m-6-a-associated-single-nucleotide-polymorphisms-in-the-lipid-loci
#9
Xingbo Mo, Shufeng Lei, Yonghong Zhang, Huan Zhang
N6-methyladenosine (m6 A) plays critical roles in many fundamental biological processes and a variety of diseases. The aim of this study was to investigate the effect of m6 A-SNPs on lipid levels. We examined the association of m6 A-SNPs with lipid levels in a genome-wide association studies (GWAS) of 188,578 individuals. Furthermore, we performed expression quantitative trait loci and differential expression analyses to add additional information for the identified m6 A-SNPs. We found 1,655 m6 A-SNPs in the GWAS dataset...
September 27, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30250149/economic-burden-of-adverse-drug-reactions-and-potential-for-pharmacogenomic-testing-in-singaporean-adults
#10
Sze Ling Chan, Hong Yen Ng, Cynthia Sung, Alexandre Chan, Michael D Winther, Liam R Brunham, Hwee-Lin Wee
Adverse drug reactions (ADRs) contribute to hospitalization but data on its economic burden is scant. Pre-emptive pharmacogenetic (PGx) testing can potentially reduce ADRs and its associated costs. The objectives of this study were to quantify the economic burden of ADRs and to estimate the breakeven cost of pre-emptive PGx testing in Singapore. We collected itemized costs for 1000 random non-elective hospitalizations of adults admitted to a tertiary-care general hospital in Singapore. The presence of ADRs at admission and their clinical characteristics were reported previously...
September 24, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30250148/association-between-slco1b1-t521c-polymorphism-and-risk-of-statin-induced-myopathy-a-meta-analysis
#11
Qian Xiang, Shu-Qing Chen, Ling-Yue Ma, Kun Hu, Zhuo Zhang, Guang-Yan Mu, Qiu-Fen Xie, Xiao-Dan Zhang, Yi-Min Cui
Numerous studies have illustrated the relationship between SLCO1B1 T521C polymorphism and statin-induced myopathy risk; however, this association is not consistent. Three electronic databases (PubMed, EMBASE, and the Cochrane Library) were searched from inception to October 2017 to identify potential studies. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated from different genetic models by using a random-effects model. Fourteen studies comprising 3265 myopathy patients and 7743 controls were included...
September 24, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30242287/association-between-hla-b-5901-and-methazolamide-induced-stevens-johnson-syndrome-toxic-epidermal-necrolysis-a-systematic-review-and-meta-analysis
#12
Wimonchat Tangamornsuksan, Manupat Lohitnavy
Methazolamide-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are life-threatening adverse drug reactions. Based on previous studies, HLA genotypes may play an important role in methazolamide-induced SJS/TEN. Therefore, to identify the associations between HLA genotypes and methazolamide-induced cutaneous adverse drug reactions (cADRs) (i.e., SJS/TEN and hypersensitivity syndrome), a systematic review and meta-analysis were performed. Two studies (one study in Korean and another in Han Chinese) met the inclusion criteria...
September 21, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30237584/genome-wide-association-analysis-of-common-genetic-variants-of-resistant-hypertension
#13
Nihal El Rouby, Caitrin W McDonough, Yan Gong, Leslie A McClure, Braxton D Mitchell, Richard B Horenstein, Robert L Talbert, Dana C Crawford, Matthew A Gitzendanner, Atsushi Takahashi, Toshihiro Tanaka, Michiaki Kubo, Carl J Pepine, Rhonda M Cooper-DeHoff, Oscar R Benavente, Alan R Shuldiner, Julie A Johnson
Resistant hypertension (RHTN), defined as uncontrolled blood pressure (BP) ≥ 140/90 using three or more drugs or controlled BP (<140/90) using four or more drugs, is associated with adverse outcomes, including decline in kidney function. We conducted a genome-wide association analysis in 1194 White and Hispanic participants with hypertension and coronary artery disease from the INternational VErapamil-SR Trandolapril STudy-GENEtic Substudy (INVEST-GENES). Top variants associated with RHTN at p < 10-4 were tested for replication in 585 White and Hispanic participants with hypertension and subcortical strokes from the Secondary Prevention of Subcortical Strokes GENEtic Substudy (SPS3-GENES)...
September 20, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30237583/an-exploratory-study-by-dmet-array-identifies-a-germline-signature-associated-with-imatinib-response-in-gastrointestinal-stromal-tumor
#14
Gloria Ravegnini, Milena Urbini, Vittorio Simeon, Chiara Genovese, Annalisa Astolfi, Margherita Nannini, Lidia Gatto, Maristella Saponara, Manuela Ianni, Valentina Indio, Giovanni Brandi, Stefania Trino, Patrizia Hrelia, Guido Biasco, Sabrina Angelini, Maria A Pantaleo
Imatinib represents the standard therapy for gastrointestinal stromal tumor (GIST) patients with metastatic/unresectable disease. Despite  the excellent results achieved with its introduction, the majority of patients quite invariably experience disease progression. The aim of this study was to understand the contribution of germline DNA polymorphisms in discriminating between imatinib clinical response [evaluated as progression free survival (PFS)] and toxicity. In particular, a discovery cohort (34 GIST with a KIT exon 11 primary mutation, and no toxicity) was analyzed through DMET array that interrogates 1936 variants in 231 genes of the ADME process...
September 20, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30237582/hla-c-12-02-is-strongly-associated-with-xuesaitong-induced-cutaneous-adverse-drug-reactions
#15
Sijia Yan, Hao Xiong, Fengmin Shao, Wen Zhang, Fanping Yang, Zheng Qi, Shengan Chen, Lin He, Menglin Jiang, Yu Su, Huizhong Zhu, Shengying Qin, Qinyuan Zhu, Xiaoqun Luo, Qinghe Xing
Xuesaitong (XST) is mainly used to treat cardiovascular and cerebrovascular diseases, sometimes causing cutaneous adverse drug reactions (cADRs) with unknown mechanisms of pathogenicity or risk factors. We aimed to verify whether human leukocyte antigen (HLA) alleles are associated with XST-related cADRs in Han Chinese population. We carried out an association study including 12 subjects with XST-induced cADRs, 283 controls, and 28 XST-tolerant subjects. Five out of 12 patients with XST-induced cADRs carried HLA-C*12:02, and all of them received XST via intravenous drip...
September 20, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30237581/genetic-markers-in-methotrexate-treatments
#16
REVIEW
Andrea Giletti, Patricia Esperon
Methotrexate (MTX), a structural analog of folic acid, is widely employed in the treatment of different cancers and autoimmune diseases. Despite the successful results observed, the main disadvantage lies in interpatient variability in the pharmacokinetic and pharmacodynamic parameters. In particular, adverse events and toxicities induced by MTX are a matter of concern and can be the cause of dose reduction or treatment discontinuation. Among the different approaches to reduce MTX therapeutic limitations, pharmacogenomics contributes by considering the effect of inherited genetic differences on those parameters...
September 20, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30214008/whole-genome-sequencing-identifies-high-impact-variants-in-well-known-pharmacogenomic-genes
#17
Jihoon Choi, Kelan G Tantisira, Qing Ling Duan
More than 1100 genetic loci have been correlated with drug response outcomes but disproportionately few have been translated into clinical practice. One explanation for the low rate of clinical implementation is that the majority of associated variants may be in linkage disequilibrium (LD) with the causal variants, which are often elusive. This study aims to identify and characterize likely causal variants within well-established pharmacogenomic genes using next-generation sequencing data from the 1000 Genomes Project...
September 14, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30206300/concordance-between-glucose-6-phosphate-dehydrogenase-g6pd-genotype-and-phenotype-and-rasburicase-use-in-patients-with-hematologic-malignancies
#18
Katherine M Robinson, Wenjian Yang, Cyrine E Haidar, Jane S Hankins, Dennis W Jay, Nancy Kornegay, Jeffrey E Rubnitz, Ulrich Broeckel, Cheng Cheng, Ching-Hon Pui, Sima Jeha, Mary V Relling
Phenotypic rather than genotypic tests remain the gold standard for diagnosing glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, with increasing use of genomic arrays and whole exome or genome sequencing, G6PD genetic data are increasingly available. We examined the utility of G6PD genetic data in patients with hematologic malignancies and the association of G6PD genotype and phenotype with rasburicase-induced methemoglobinemia. We analyzed G6PD activity for 990 patients. Genotype data were available from the Affymetrix DMET array (n = 379), whole exome sequencing (n = 374), and/or the Illumina exome array (n = 634) for 645 patients...
September 12, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30206299/an-optimized-prediction-framework-to-assess-the-functional-impact-of-pharmacogenetic-variants
#19
Yitian Zhou, Souren Mkrtchian, Masaki Kumondai, Masahiro Hiratsuka, Volker M Lauschke
Prediction of phenotypic consequences of mutations constitutes an important aspect of precision medicine. Current computational tools mostly rely on evolutionary conservation and have been calibrated on variants associated with disease, which poses conceptual problems for assessment of variants in poorly conserved pharmacogenes. Here, we evaluated the performance of 18 current functionality prediction methods leveraging experimental high-quality activity data from 337 variants in genes involved in drug metabolism and transport and found that these models only achieved probabilities of 0...
September 12, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30206298/a-genome-wide-association-and-admixture-mapping-study-of-bronchodilator-drug-response-in-african-americans-with-asthma
#20
Melissa L Spear, Donglei Hu, Maria Pino-Yanes, Scott Huntsman, Celeste Eng, Albert M Levin, Victor E Ortega, Marquitta J White, Meghan E McGarry, Neeta Thakur, Joshua Galanter, Angel C Y Mak, Sam S Oh, Elizabeth Ampleford, Stephen P Peters, Adam Davis, Rajesh Kumar, Harold J Farber, Kelley Meade, Pedro C Avila, Denise Serebrisky, Michael A Lenoir, Emerita Brigino-Buenaventura, William Rodriguez Cintron, Shannon M Thyne, Jose R Rodriguez-Santana, Jean G Ford, Rocio Chapela, Andrés Moreno Estrada, Karla Sandoval, Max A Seibold, Cheryl A Winkler, Eugene R Bleecker, Deborah A Myers, L Keoki Williams, Ryan D Hernandez, Dara G Torgerson, Esteban G Burchard
Short-acting β2 -adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma. To identify genetic variants that may contribute to differences in BDR in African Americans with asthma, we performed a genome-wide association study (GWAS) of BDR in 949 African-American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase III genotypes...
September 12, 2018: Pharmacogenomics Journal
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