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Pharmacogenomics Journal

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
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
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
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
Sètondji Cocou Modeste Alexandre Yahouédéhou, Elisângela Vitória Adorno, Caroline Conceição da Guarda, Uche Samuel Ndidi, Suellen Pinheiro Carvalho, Rayra Pereira Santiago, Milena Magalhães Aleluia, Rodrigo Mota de Oliveira, Marilda de Souza Gonçalves
Hydroxyurea (HU) was approved to be used in the treatment of sickle cell disease (SCD) because of its anti-sickling potential. However, there is variability in HU response among SCD patients and this can be due to physiological, socioeconomic, environmental, metabolic and/or genetic factors. The present review focuses on the latter two. Three quantitative trait loci, HBG2, BCL11A and HMIP, have been suggested as important markers for HU response. Other genes (ASS1, KLF10, HAO2, MAP3K5, PDE7B, TOX, NOS1, NOS2A, FLT1, ARG1, ARG2, UGT1A1, OR51B5/6, SIN3A, SALL2, SAR1A, UTB, OCTN1, CYP2C9, AQP9, MPO, CYP2E1, and GSTT1) have also been considered...
September 12, 2018: Pharmacogenomics Journal
Youssef M Roman
No abstract text is available yet for this article.
September 10, 2018: Pharmacogenomics Journal
Weronika Maria Szejniuk, Ana I Robles, Tine McCulloch, Ursula Gerda Inge Falkmer, Oluf Dimitri Røe
Platinum-based chemotherapy is commonly used to treat non-small cell lung cancer (NSCLC). However, its efficacy is limited and no molecular biomarkers that predict response are available. In this review, we summarize current knowledge concerning potential epigenetic predictive markers for platinum-based chemotherapy response in NSCLC. A systematic search of PubMed and using keywords "non-small cell lung cancer" combined with "chemotherapy predictive biomarkers", "chemotherapy epigenetics biomarkers", "chemotherapy microRNA biomarkers", "chemotherapy DNA methylation" and "chemotherapy miRNA biomarkers" revealed 1740 articles from PubMed and 36 clinical trials...
September 7, 2018: Pharmacogenomics Journal
Eric Huang, Nuwan C Hettige, Gwyneth Zai, Julia Tomasi, Justin Huang, Clement C Zai, Nela Pivac, Matea Nikolac Perkovic, Arun K Tiwari, James L Kennedy
Brain-derived neurotrophic factor (BDNF) plays an important role in dopaminergic and serotonergic neurotransmission by modulating dopaminergic neuron differentiation and establishment. Multiple studies have analyzed the functional BDNF Val66Met variant in relation to antipsychotic response in schizophrenia (SCZ) patients, yielding mixed results. A meta-analysis was thus performed to examine the relationship between this variant and symptom improvement during antipsychotic treatment. Searches using PubMed, Web of Science, and PsycInfo until October 2017 yielded 11 studies that met inclusion criteria (total n = 3774)...
September 5, 2018: Pharmacogenomics Journal
Jonathan Massey, Darren Plant, Kimme Hyrich, Ann W Morgan, Anthony G Wilson, Athina Spiliopoulou, Marco Colombo, Paul McKeigue, John Isaacs, Heather Cordell, Costantino Pitzalis, Anne Barton
Rheumatoid arthritis (RA) is characterised by chronic synovial joint inflammation. Treatment has been revolutionised by tumour necrosis factor alpha inhibitors (TNFi) but each available drug shows a significant non-response rate. We conducted a genome-wide association study of 1752 UK RA TNFi-treated patients to identify predictors of change in the Disease Activity Score 28 (DAS28) and subcomponents over 3-6 months. The rs7195994 variant at the FTO gene locus was associated with infliximab response when looking at a change in the swollen joint count (SJC28) subcomponent (p = 9...
August 31, 2018: Pharmacogenomics Journal
Sheila Garcia-Rosa, Daniela Bb Trivella, Vanessa D Marques, Rodolfo B Serafim, José Gc Pereira, Julio Cc Lorenzi, Greice A Molfetta, Paulo P Christo, Guilherme S Olival, Vania Bt Marchitto, Doralina G Brum, Thais S Sabedot, Houtan Noushmehr, Alessandro S Farias, Leonilda Mb Santos, José A Nogueira-Machado, Jorge Es Souza, Camila M Romano, Rodrigo M Conde, Antonio C Santos, Carlos T Guerreiro, Willem H Schreuder, Frederico O Gleber-Netto, Maria Amorim, Renan Valieris, Israel Tojal da Silva, Wilson A Silva, Diana N Nunes, Paulo Sl Oliveira, Valeria Valente, Maria Augusta Arruda, Stephen J Hill, Amilton A Barreira, Emmanuel Dias-Neto
Multiple Sclerosis (MS) is an inflammatory neurodegenerative disease that affects approximately 2.5 million people globally. Even though the etiology of MS remains unknown, it is accepted that it involves a combination of genetic alterations and environmental factors. Here, after performing whole exome sequencing, we found a MS patient harboring a rare and homozygous single nucleotide variant (SNV; rs61745847) of the G-protein coupled receptor (GPCR) galanin-receptor 2 (GALR2) that alters an important amino acid in the TM6 molecular toggle switch region (W249L)...
August 22, 2018: Pharmacogenomics Journal
Nyarai Desiree Soko, Emile Chimusa, Collen Masimirembwa, Collet Dandara
Studies in Caucasian and Asian populations consistently associated interindividual and interethnic variability in rosuvastatin pharmacokinetics to the polymorphisms SLCO1B1 c.521T>C (rs4149056 p. Val174Ala) and ABCG2 c.421C>A (rs2231142, p. Gln141Lys). To investigate the pharmacogenetics of rosuvastatin in African populations, we first screened 785 individuals from nine ethnic African populations for the SLCO1B1 c.521C and ABCG2 c.421CA variants. This was followed by sequencing whole exomes from individuals of African Bantu descent, who participated in a 20 mg rosuvastatin pharmacokinetic trial in Harare Zimbabwe...
August 13, 2018: Pharmacogenomics Journal
Michael Erlichster, Benjamin Goudey, Efstratios Skafidas, Patrick Kwan
Reduction of adverse drug reaction (ADR) incidence through screening of predisposing human leucocyte antigen (HLA) alleles is a promising approach for many widely used drugs. However, application of these associations has been limited by the cost burden of HLA genotyping. Use of single nucleotide polymorphisms (SNPs) that can approximate ('tag') HLA alleles of interest has been proposed as a cost-effective and simple alternative to conventional genotyping. However, most reported SNP tags have not been validated and there is concern regarding clinical utility of this approach due to tagging inconsistency across different populations...
August 10, 2018: Pharmacogenomics Journal
James R Perkins, Marialbert Acosta-Herrera, María C Plaza-Serón, Raquel Jurado-Escobar, Inmaculada Doña, Elena García-Martín, María Isidoro-García, Joan Bartra, David Ribas-Perez, Cristobalina Mayorga, María J Torres, Carlos Flores, José A Cornejo-García
Non-steroidal anti-inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity reactions. Such reactions can be pharmacologically or immunologically mediated, but in both cases individual susceptibility can be influenced by genetic factors. Polymorphisms in centrosomal protein of 68 kDa (CEP68) have been associated with pharmacologically mediated NSAIDs reactions. Here, we evaluated this gene in immunologically mediated single-NSAID-induced urticaria/angioedema or anaphylaxis (SNIUAA) by analyzing 52 single nucleotide polymorphisms in CEP68 in 176 patients and 363 NSAIDs-tolerant controls...
August 10, 2018: Pharmacogenomics Journal
Pınar Akın Kabalak, İsmail Savaş, Nejat Akar, Nalan Demir, Yonca Eğin
Warfarin works by inhibiting VKORC1, so polymorphisms of this gene modify the required drug dose. The aim of this study is to examine the relation between therapeutic weekly dose of warfarin and C1173T/G1639A polymorphism of VKORC1 in patients with VTE. Seventy-five patients with VTE were enrolled. Weekly warfarin doses and time (day) to reach therapeutic INR were evaluated retrospectively along with VKORC1-C1173T and G1639A alleles. The mean weekly warfarin dose was lower and time to reach therapeutic INR was shorter in homozygote alleles (AA and TT) (p < 0...
August 10, 2018: Pharmacogenomics Journal
Zhifu Wang, Zhaohui Liu, Wenyao Wang, Yuanyuan Fu, Wen Chen, Wenke Li, Xue Zhang, Yida Tang, Zhou Zhou
The effect of dual antiplatelet therapy, clopidogrel combined with aspirin, was influenced by CYP2C19 gene mutation and heterogeneity of population. Related studies remained controversial and limited, especially in Chinese. Total 3295 unrelated ACS Chinese patients undergoing percutaneous coronary intervention (PCI) were recruited and followed up to 1 year. Meanwhile, baseline and clinical data were retrieved. CYP2C19*2 and *3 were genotyped by sequencing. Associations of variants and metabolic types with platelet reactivity (PR) were analyzed by a logistic regression model...
July 31, 2018: Pharmacogenomics Journal
M Gaibar, A Novillo, A Romero-Lorca, M E Esteban, A Fernández-Santander
No abstract text is available yet for this article.
July 31, 2018: Pharmacogenomics Journal
Kevin S O'Connell, Nathaniel W McGregor, Anil Malhotra, Todd Lencz, Robin Emsley, Louise Warnich
Voltage-gated calcium channels have been implicated in schizophrenia aetiology; however, little is known about their involvement in antipsychotic treatment response. This study investigated variants within the calcium channel subunit genes for association with antipsychotic treatment response in a first episode schizophrenia cohort. Twelve regulatory variants within seven genes were shown to be significantly associated with treatment outcome. Most notably, the CACNA1B rs2229949 CC genotype was associated with improved negative symptomology, where the C allele was predicted to abolish a miRNA-binding site (has-mir-5002-3p), suggesting a possible mechanism of action through which this variant may have an effect...
July 22, 2018: Pharmacogenomics Journal
Yaowaluck Hongkaew, Sadeep Medhasi, Ekawat Pasomsub, Nattawat Ngamsamut, Apichaya Puangpetch, Natchaya Vanwong, Monpat Chamnanphon, Penkhae Limsila, Chuthamanee Suthisisang, Bob Wilffert, Chonlaphat Sukasem
The aim of this study was to investigate the association of drug-metabolizing enzyme and transporter (DMET) polymorphisms with the risperidone-induced prolactin response using an overlapping gene model between serum prolactin level and hyperprolactinemia in autism spectrum disorder (ASD) patients. Eighty-four ASD patients who were receiving risperidone for at least 1 month were recruited and then assigned to either the normal prolactin group or the hyperprolactinemia group based on their serum prolactin level...
June 29, 2018: Pharmacogenomics Journal
Mitsukuni Suenaga, Marta Schirripa, Shu Cao, Wu Zhang, Dongyun Yang, Chiara Cremolini, Sara Lonardi, Francesca Bergamo, Yang Ning, Noriko Yamamoto, Satoshi Okazaki, Martin D Berger, Yuji Miyamoto, Roel Gopez, Afsaneh Barzi, Toshiharu Yamaguchi, Sebastian Stintzing, Volker Heinemann, Fotios Loupakis, Alfredo Falcone, Heinz-Josef Lenz
PIN1-mediated substrate isomerization plays a role in the repair of DNA double-strand breaks. We hypothesized that genetic polymorphisms in PIN1-related pathways may affect tumor sensitivity to oxaliplatin or irinotecan in metastatic colorectal cancer (mCRC) patients. We analyzed genomic DNA from five cohorts of mCRC patients (total 950) treated with different first-line treatments: oxaliplatin cohorts 1 (n = 146) and 2 (n = 70); irinotecan cohorts 1 (n = 228), and 2 (n = 276); and combination cohort (n = 230)...
June 21, 2018: Pharmacogenomics Journal
John C Taylor, Tim Bongartz, Jonathan Massey, Borbala Mifsud, Athina Spiliopoulou, Ian C Scott, Jianmei Wang, Michael Morgan, Darren Plant, Marco Colombo, Peter Orchard, Sarah Twigg, Iain B McInnes, Duncan Porter, Jane E Freeston, Jackie L Nam, Heather J Cordell, John D Isaacs, Jenna L Strathdee, Donna Arnett, Maria J H de Hair, Paul P Tak, Stella Aslibekyan, Ronald F van Vollenhoven, Leonid Padyukov, S Louis Bridges, Costantino Pitzalis, Andrew P Cope, Suzanne M M Verstappen, Paul Emery, Michael R Barnes, Felix Agakov, Paul McKeigue, Taisei Mushiroda, Michiaki Kubo, Richard Weinshilboum, Anne Barton, Ann W Morgan, Jennifer H Barrett
Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28)...
July 2018: Pharmacogenomics Journal
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