Read by QxMD icon Read


Jiazhen Liu, Carol Friedman, Joseph Finkelstein
Medication regimen may be optimized based on individual drug efficacy identified by pharmacogenomic testing. However, majority of current pharmacogenomic decision support tools provide assessment only of single drug-gene interactions without taking into account complex drug-drug and drug-drug-gene interactions which are prevalent in people with polypharmacy and can result in adverse drug events or insufficient drug efficacy. The main objective of this project was to develop comprehensive pharmacogenomic decision support for medication risk assessment in people with polypharmacy that simultaneously accounts for multiple drug and gene effects...
2018: AMIA Summits on Translational Science Proceedings
Seung-Been Lee, Marsha M Wheeler, Karynne Patterson, Sean McGee, Rachel Dalton, Erica L Woodahl, Andrea Gaedigk, Kenneth E Thummel, Deborah A Nickerson
PURPOSE: Genotyping CYP2D6 is important for precision drug therapy because the enzyme it encodes metabolizes approximately 25% of drugs, and its activity varies considerably among individuals. Genotype analysis of CYP2D6 is challenging due to its highly polymorphic nature. Over 100 haplotypes (star alleles) have been defined for CYP2D6, some involving a gene conversion with its nearby nonfunctional but highly homologous paralog CYP2D7. We present Stargazer, a new bioinformatics tool that uses next-generation sequencing (NGS) data to call star alleles for CYP2D6 ( https://stargazer...
June 6, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Dagmar F Hernandez-Suarez, Jonnalie C Tomassini-Fernandini, Angelica Cuevas, Anyelis N Rosario-Berrios, Héctor J Nuñez-Medina, Dariana Padilla-Arroyo, Nannette Rivera, Jennifer Liriano, Rocio K Vega-Roman, Jessicca Y Renta, Kyle Melin, Jorge Duconge
Background: Variations in several clopidogrel-pharmacogenes have been linked to clopidogrel response variability and clinical outcomes. We aimed to determine the frequency distribution of major polymorphisms on CYP2C19 , PON1 , ABCB1 and P2RY12 pharmacogenes in Puerto Ricans. Methods : This was a cross-sectional, population-based study of 200 unrelated "Guthrie" cards specimens from newborns registered in the Puerto Rican newborn screening program (PRNSP) between 2004 and 2014. Taqman® SNP assay techniques were used for genotyping...
May 30, 2018: International Journal of Environmental Research and Public Health
Ute I Schwarz, Markus Gulilat, Richard B Kim
Inherited genetic variations in pharmacogenetic loci are widely acknowledged as important determinants of phenotypic differences in drug response, and may be actionable in the clinic. However, recent studies suggest that a considerable number of novel rare variants in pharmacogenes likely contribute to a still unexplained fraction of the observed interindividual variability. Next-generation sequencing (NGS) represents a rapid, relatively inexpensive, large-scale DNA sequencing technology with potential relevance as a comprehensive pharmacogenetic genotyping platform to identify genetic variation related to drug therapy...
May 29, 2018: Cold Spring Harbor Perspectives in Medicine
Ulrich M Zanger, Kathrin Klein, Nicole Kugler, Tamara Petrikat, Chang S Ryu
Germline pharmacogenetics has so far mainly studied common variants in "pharmacogenes," i.e., genes encoding drug metabolizing enzymes and transporters (DMET genes), certain auxiliary and regulatory genes, and drug target genes. Despite remarkable progress in understanding genetically determined differences in pharmacokinetics and pharmacodynamics of drugs, currently known common variants even in important pharmacogenes explain genetic variability only partially. This suggests "missing heritability" that may in part be due to rare variants in the classical pharmacogenes, but current evidence suggests that largely unexplored resources with potential for pharmacogenetics exist, both within already known pharmacogenes and in entirely new areas...
2018: Advances in Pharmacology
Paul C D Bank, Jesse J Swen, Henk-Jan Guchelaar
Currently, germline pharmacogenomics (PGx) is successfully implemented within certain specialties in clinical care. With the integration of PGx in pharmacotherapy multiple stakeholders are involved, which are identified in this chapter. Clinically relevant pharmacogenes with their related PGx test are discussed, along with diagnostic test criteria to guide clinicians and policy makers in PGx test selection. The chapter further reviews the similarities and the differences between the guidelines of the Dutch Pharmacogenetics Working Group and the Clinical Pharmacogenetics Implementation Consortium which both support healthcare professionals in understanding PGx test results and help guiding pharmacotherapy by providing evidence-based dosing recommendations...
2018: Advances in Pharmacology
Guilherme Suarez-Kurtz, Esteban J Parra
Pharmacogenetics/pharmacogenomics (PGx) relies on human genetic diversity. In this review we initially examine the PGx implications of human demographic history and genetic diversity, and highlight results from recent studies on the worldwide distribution of common and rare variants in pharmacogenes. The abundance of rare variants implies that a substantial effort will be required to identify their putative functional effects and to develop reliable algorithms for PGx-guided prescription. Furthermore, variants in all pharmacogenes relevant to a drug treatment must be considered...
2018: Advances in Pharmacology
Magnus Ingelman-Sundberg, Souren Mkrtchian, Yitian Zhou, Volker M Lauschke
BACKGROUND: Variability in genes implicated in drug pharmacokinetics or drug response can modulate treatment efficacy or predispose to adverse drug reactions. Besides common genetic polymorphisms, recent sequencing projects revealed a plethora of rare genetic variants in genes encoding proteins involved in drug metabolism, transport, and response. RESULTS: To understand the global importance of rare pharmacogenetic gene variants, we mapped the variability in 208 pharmacogenes by analyzing exome sequencing data from 60,706 unrelated individuals and estimated the importance of rare and common genetic variants using a computational prediction framework optimized for pharmacogenetic assessments...
May 25, 2018: Human Genomics
Sek Won Kong, In-Hee Lee, Xuanshi Liu, Joel N Hirschhorn, Kenneth D Mandl
PurposeTo evaluate the coverage and accuracy of whole-exome sequencing (WES) across vendors.MethodsBlood samples from three trios underwent WES at three vendors. Relative performance of the three WES services was measured for breadth and depth of coverage. The false-negative rates (FNRs) were estimated using the segregation pattern within each trio.ResultsMean depth of coverage for all genes was 189.0, 124.9, and 38.3 for the three vendor services. Fifty-five of the American College of Medical Genetics and Genomics 56 genes, but only 56 of 63 pharmacogenes, were 100% covered at 10 × in at least one of the nine individuals for all vendors; however, there was substantial interindividual variability...
April 12, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Jiazhen Liu, Joseph Finkelstein
The main objective of this project was to introduce approaches for comprehensive medication risk assessment in people with polypharmacy that simultaneously account for multiple drug and gene effects. To achieve this goal, we developed an integrated knowledge repository of actionable pharmacogenes and a scoring algorithm that was pilot-tested using a data set containing pharmacogenomic information of people with polypharmacy. Metabolic phenotyping using resulting database demonstrated recall of 83.6% and precision of 87...
2018: Studies in Health Technology and Informatics
(no author information available yet)
No abstract text is available yet for this article.
May 2018: Pharmacogenetics and Genomics
Haifa Jmel, Lilia Romdhane, Yosra Ben Halima, Meriem Hechmi, Chokri Naouali, Hamza Dallali, Yosr Hamdi, Jingxuan Shan, Abdelmajid Abid, Henda Jamoussi, Sameh Trabelsi, Lotfi Chouchane, Donata Luiselli, Sonia Abdelhak, Rym Kefi
Genetic variation is an important determinant affecting either drug response or susceptibility to adverse drug reactions. Several studies have highlighted the importance of ethnicity in influencing drug response variability that should be considered during drug development. Our objective is to characterize the genetic variability of some pharmacogenes involved in the response to drugs used for the treatment of Metabolic Syndrome (MetS) in Tunisia and to compare our results to the worldwide populations. A set of 135 Tunisians was genotyped using the Affymetrix Chip 6...
2018: PloS One
Amy L Pasternak, Lu Zhang, Daniel L Hertz
Tacrolimus is prescribed to the majority of transplant recipients to prevent graft rejection, and although patients are maintained on oral administration, nonoral routes of administration are frequently used in the initial post-transplant period. CYP3A5 genotype is an established predictor of oral tacrolimus dose requirements, and clinical guideline recommendations exist for CYP3A5-guided dose selection. However, the association between CYP3A5 and nonoral tacrolimus administration is currently poorly understood, and differs from the oral tacrolimus relationship...
April 2018: Pharmacogenomics
Ravindran Ankathil, Husin Azlan, Abu Abdullah Dzarr, Abdul Aziz Baba
Despite the excellent efficacy and improved clinical responses obtained with imatinib mesylate (IM), development of resistance in a significant proportion of chronic myeloid leukemia (CML) patients on IM therapy have emerged as a challenging problem in clinical practice. Resistance to imatinib can be due to heterogeneous array of factors involving BCR/ABL-dependent and BCR/ABL-independent pathways. Although BCR/ABL mutation is the major contributory factor for IM resistance, reduced bio-availability of IM in leukemic cells is also an important pharmacokinetic factor that contributes to development of resistance to IM in CML patients...
April 2018: Pharmacogenomics
Prema S Rao, Ryan Endicott, Randy Mullins, U Subrahmanyeswara Rao
Comparison of human genome sequences from different individuals has unraveled that genes involved in the drug efficacy and metabolism are polymorphic, harboring mutations, splicing variations and other alterations. These data provide a reasonable explanation for the inter-individual variations observed in drug therapy. Thus, a detailed molecular analysis and an in-depth knowledge of these genes is a prerequisite to practice pharmacogenomics-based medicine. We have introduced a 6-week laboratory research rotation to train students in the expression analysis of different pharmacogenes combined with bioinformatics tools...
March 8, 2018: Pharmacogenomics Journal
Carrie C Hoefer, Emily J Brick, Ann Savariar, David F Kisor, Amy Dawson, Ahmad Khatri, Brian Henriksen
AIM: The aim of this study was to investigate 60 SNPs pertaining to drug metabolism and pharmacodynamics in the Burmese refugee population in the Fort Wayne, Indiana area to better inform patient care. MATERIALS & METHODS: Sixty-two self-identified Burmese refugees were genotyped for 60 common SNPs pertaining to pharmacokinetic and pharmacodynamic pharmacogenes. The resulting allelic frequencies were compared with Ensembl's database for surrounding populations to Myanmar and America...
April 2018: Pharmacogenomics
Ibrahim Numanagić, Salem Malikić, Michael Ford, Xiang Qin, Lorraine Toji, Milan Radovich, Todd C Skaar, Victoria M Pratt, Bonnie Berger, Steve Scherer, S Cenk Sahinalp
High-throughput sequencing provides the means to determine the allelic decomposition for any gene of interest-the number of copies and the exact sequence content of each copy of a gene. Although many clinically and functionally important genes are highly polymorphic and have undergone structural alterations, no high-throughput sequencing data analysis tool has yet been designed to effectively solve the full allelic decomposition problem. Here we introduce a combinatorial optimization framework that successfully resolves this challenging problem, including for genes with structural alterations...
February 26, 2018: Nature Communications
Richard Meier, Chengpeng Bi, Roger Gaedigk, Daniel P Heruth, Shui Qing Ye, J Steven Leeder, Brooke L Fridley
OBJECTIVES: The majority of drug dosing studies are based on adult populations, with modification of the dosing for children based on size and weight. This rudimentary approach for drug dosing children is limited, as biologically a child can differ from an adult in far more aspects than just size and weight. Specifically, understanding the ontogeny of childhood liver development is critical in dosing drugs that are metabolized through the liver, as the rate of metabolism determines the duration and intensity of a drug's pharmacologic action...
March 2018: Pharmacogenetics and Genomics
Bani Tamraz, Yong Huang, Audrey L French, Seble Kassaye, Kathryn Anastos, Marek J Nowicki, Stephen Gange, Deborah R Gustafson, Peter Bacchetti, Ruth M Greenblatt, Pirro G Hysi, Bradley E Aouizerat
Hair provides a direct measure of long-term exposure of atazanavir (ATV). We report the results of the first genome-wide association study (GWAS) of ATV exposure measured in hair in an observational cohort representative of US women living with HIV; the Women's Interagency HIV Study. Approximately 14.1 million single nucleotide polymorphisms (SNPs) were analyzed in linear regression-based GWAS, with replication, adjusted for nongenetic predictors collected under conditions of actual use of ATV in 398 participants...
January 9, 2018: Clinical Pharmacology and Therapeutics
María Santos, Mikko Niemi, Masahiro Hiratsuka, Masaki Kumondai, Magnus Ingelman-Sundberg, Volker M Lauschke, Cristina Rodríguez-Antona
PurposeVariability in pharmacokinetics and drug response is shaped by single-nucleotide variants (SNVs) as well as copy-number variants (CNVs) in genes with importance for drug absorption, distribution, metabolism, and excretion (ADME). While SNVs have been extensively studied, a systematic assessment of the CNV landscape in ADME genes is lacking.MethodsWe integrated data from 2,504 whole genomes from the 1000 Genomes Project and 59,898 exomes from the Exome Aggregation Consortium to identify CNVs in 208 relevant pharmacogenes...
October 26, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"