Pharmacogenetics and Drug Metabolism

Drug-induced cis-regulatory elements in human hepatocytes affect molecular phenotypes associated with adverse reactions

The paper identifies drug-induced cis-regulatory elements in human hepatocytes that influence molecular phenotypes linked to adverse drug reactions.

Association Analysis of CYP2A6 Gene Variant (rs1801272A>T) with Nicotine Metabolism and Smoking Tendency Among Pakistani Youth

The paper examines the association of CYP2A6 rs1801272A>T variant with nicotine metabolism and smoking tendency in Pakistani youth using ARMS PCR and PLINK, finding a non-significant trend and higher odds for carriers.

Local ancestry informed GWAS of warfarin dose requirement in African Americans identifies a novel CYP2C19 splice QTL

Population-specific Risk of Pharmacogenomics-related Inaccurate Drug Dosing of ICU Patients

The paper assesses genetic risks of inaccurate ICU drug dosing in Qataris by analyzing whole genome sequencing data and identifies population-specific pharmacogenomics variants.

Effects of alcohol consumption and tobacco smoking on the composition of the ensemble of drug metabolizing enzymes and transporters in human liver

This study investigates how alcohol consumption and smoking affect drug-metabolizing enzymes and transporters in human liver microsomes, identifying significant changes in enzyme abundance and proposing an alcohol exposure index.

Stable lentiviral-mediated expression of Cytochrome P450 2D6 in HepaRG cells: New means for in vitro assessment of xenobiotic biotransformation and cytotoxicity

This paper develops a method to enhance CYP2D6 expression in HepaRG cells using lentiviral transduction, demonstrating improved drug metabolism and toxicity assessment capabilities.

Species Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with in Vivo Anti-alphaviral Activity

This study evaluates the species-dependent metabolism and pharmacokinetics of a covalent nsP2 protease inhibitor, showing rapid clearance in mice but antiviral efficacy, and suggests potential for human dosing.

Exploring Youth-Perceived Barriers and Attitudes Towards the Clinical Use of Pharmacogenetic Testing to Optimise Antidepressant Pharmacotherapy

This study explores youth perceptions of barriers and attitudes towards pharmacogenetic testing for antidepressant treatment optimization in primary care.

Clinically actionable pharmacogenomic landscape of antidepressants and antipsychotics in Qatar: A population-based cohort study

This study identifies actionable genetic variants in Qatar's population for antidepressants and antipsychotics, revealing high prevalence of metabolizer phenotypes impacting drug response.

Computational Analysis of the Gut Microbiota-Mediated Drug Metabolism

This study introduces a computational framework, MDM, to predict gut microbiota-mediated drug metabolism by integrating diverse datasets and existing tools to identify potential metabolites and their associated enzymes.

StarPhase: Comprehensive Phase-Aware Pharmacogenomic Diplotyper for Long-Read Sequencing Data

StarPhase diplotypes 21 pharmacogenes using long-read sequencing with high accuracy, updating 26.2% of existing diplotypes and highlighting gaps in pharmacogenomic databases.

CLINICAL IMPLEMENTATION OF PREEMPTIVE PHARMACOGENOMICS TESTING FOR PERSONALIZED MEDICINE AT AN ACADEMIC MEDICAL CENTER

This paper describes the implementation of preemptive pharmacogenomics testing linked to an electronic clinical decision support system at UCSF Health to guide medication decisions.

Identifying Opioid-Related Pharmacogenomic Variants in High-Risk Hospitalized Infants: A Pilot Study

This study identifies opioid-related pharmacogenomic variants in high-risk hospitalized infants, finding higher homozygosity for ABCB1 variants and lower for COMT and OPRM1 compared to a general population database.

Utilization of a Human Liver Tissue Chip for Drug-Metabolizing Enzyme Induction Studies of Perpetrator and Victim Drugs

This study uses a human liver tissue chip to assess drug-drug interactions by evaluating perpetrator and victim drug metabolism over 4 weeks.

Genetic ancestral patterns in CYP2D6 alleles: structural variants, rare variants, and clinical associations in 479,144 UK Biobank genomes

The paper analyzes CYP2D6 genetic variation across 479,144 UK Biobank genomes, identifying structural and rare variants, and their clinical associations across ancestries.

Meta-analysis of CYP2C19 and CYP2D6 metabolic activity on antidepressant response from 13 clinical studies using genotype imputation

This study examines the association between CYP2C19 and CYP2D6 metabolic phenotypes and antidepressant response using genotype imputation across 13 studies, finding no significant associations after correction for multiple testing.

Non-additivity of the functional properties of individual P450 species and its manifestation in the effects of alcohol consumption on the metabolism of ketamine and amitriptyline

The paper investigates how alcohol affects drug metabolism by analyzing interactions between P450 enzymes in human liver microsomes, finding alcohol increases low-affinity enzyme roles and alters enzyme-specific metabolic rates.

Frequency of pharmacogenomic variation and medication exposures among All of Us Participants

The paper assesses pharmacogenomic variation and medication exposures in a diverse cohort using whole genome sequencing and EHR data, finding high prevalence of actionable variants and previously unreported alleles.

ursaPGx: a new R package to annotate pharmacogenetic star alleles using phased whole genome sequencing data

Development and validation of a pharmacogenomics reporting workflow based on the Illumina Global Screening Array chip

The paper validates a pharmacogenomics reporting workflow using the Illumina Global Screening Array for 25 genes, showing high accuracy and reproducibility across multiple reference datasets.

Rare Variants in Pharmacogenes Influence Clozapine Metabolism in Individuals with Schizophrenia

This study identifies rare genetic variants in pharmacogenes that influence clozapine metabolism in schizophrenia patients, with CYP1A2 variants showing the strongest effect.

Star allele search: a pharmacogenetic annotation database and user-friendly search tool of publicly available 1000 Genomes Project biospecimens

The paper introduces a pharmacogenetic annotation database and search tool for 1000 Genomes Project biospecimens, enabling allele haplotype and diplotype analysis and supporting clinical PGx assay development.

The variation landscape of CYP2D6 in a multi-ethnic Asian population

The paper analyzes CYP2D6 variation in a multi-ethnic Asian cohort, identifying population-specific star alleles and actionable variants with implications for pharmacogenomics.

Signatures of co-evolution and co-regulation in the CYP3A and CYP4F genes in humans

This study identifies co-evolution and co-regulation in CYP3A and CYP4F genes across human populations, linking genetic diversity to drug metabolism and health outcomes.

Deep mutational scanning of CYP2C19 reveals a substrate specificity-abundance tradeoff

The paper uses deep mutational scanning to analyze CYP2C19 variants, revealing a tradeoff between substrate specificity and protein abundance.

PharmGScore scores of compound genetic variant burden for psychiatric treatment optimization

This paper introduces PharmGScore, a genetic variant burden scoring system for antidepressant response, showing it outperforms existing methods and identifies gene associations with antidepressant toxicity.

Sex-biased gene expression and gene-regulatory networks of sex-biased adverse event drug targets and drug metabolism genes

The paper identifies sex-biased adverse event drug targets and metabolism genes, showing their sex-specific gene expression and regulatory networks.

A physiologically based pharmacokinetic model for CYP2E1 phenotyping via chlorzoxazone

This study develops a PBPK model to assess CYP2E1 activity using chlorzoxazone, showing how ethanol consumption, abstinence, and liver impairment affect its metabolism.

Haplotype phasing of CYP2D6: an allelic ratio method using Agena MassARRAY data

This paper introduces a new protocol for CYP2D6 haplotype phasing using Agena MassARRAY data, achieving 100% concordance with prior data and resolving copy numbers in some reference samples.

Pharmacogenetic allele variant frequencies: An analysis of the VAs Million Veteran Program (MVP) as a representation of the diversity in US population.

The paper analyzes pharmacogenetic variant frequencies in the MVP dataset to represent US population diversity across different ancestries.