4.7 Article

A frequent CYP2D6 variant promotes skipping of exon 3 and reduces CYP2D6 protein expression in human liver samples

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Article Pharmacology & Pharmacy

Cross-Ancestry Genome-Wide Association Study Defines the Extended CYP2D6 Locus as the Principal Genetic Determinant of Endoxifen Plasma Concentrations

Chiea Chuen Khor et al.

Summary: The extended CYP2D6 locus at 22q13 is the principal genetic determinant of endoxifen plasma concentration, as revealed by the first cross-ancestry genome-wide association study. Functional analysis showed that 66% of the associated variants in this region were significantly correlated with hepatic CYP2D6 activity or expression. Machine learning models demonstrated that hotspot variants in this region, combined with CYP2D6 activity score, could explain a significant portion of the variability in tamoxifen metabolites.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2023)

Article Pharmacology & Pharmacy

The Impact of the CYP2D6 Enhancer Single Nucleotide Polymorphism on CYP2D6 Activity

Jean C. Dinh et al.

Summary: Research on the impact of the enhancer SNP rs5758550 on CYP2D6 activity suggests minimal effects on activity prediction, with potential substrate-dependency for certain probe substrates. Although in vitro studies found a modestly higher metabolite formation rate for CYP2D6*2 alleles with the enhancer SNP, the lack of significant effect in vivo raises questions on whether the observed effects are truly caused by the enhancer SNP. Further investigation is needed to determine the exact role of this SNP in CYP2D6 pharmacogenetic testing.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2022)

Article Pharmacology & Pharmacy

Quantification ofIn VivoMetabolic Activity ofCYP2D6Genotypes and Alleles Through Population Pharmacokinetic Analysis of Vortioxetine

Trine Frederiksen et al.

Summary: The study aimed to quantify the in vivo CYP2D6 activity of different CYP2D6 alleles and genotypes through population pharmacokinetic modeling, revealing differences in CYP2D6 activity levels among subjects categorized as CYP2D6 intermediate metabolizers. Additionally, the study identified varying levels of reduction in CYP2D6 activity associated with decreased function alleles, with significant differences observed in the activity of different alleles such as CYP2D6*10 compared to CYP2D6*17 and CYP2D6*41. Further discussions on current CYP2D6 genotype-phenotype classification systems, especially regarding decreased function alleles and the IM phenotype, are warranted based on these results.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2021)

Article Pharmacology & Pharmacy

Tri-Allelic Haplotypes Determine and Differentiate Functionally Normal Allele CYP2D6*2 and Impaired Allele CYP2D6*41

Ulrich M. Zanger et al.

Summary: CYP2D6 metabolizes a significant portion of clinically used drugs, with its genetic polymorphism playing a key role in drug safety and efficacy. The study identified specific genetic variants causing functional differences between the common alleles *2 and *41, highlighting the importance of considering triple haplotypes in explaining these differences for clinical implementation of CYP2D6 pharmacogenetics.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2021)

Article Genetics & Heredity

Relationships betweenCYP1A2,CYP2C9,CYP2C19,CYP2D6andCYP3A4metabolic phenotypes and genotypes in a Nicaraguan Mestizo population

Fernando de Andres et al.

Summary: This study found significant differences between CYP450 genotypes and metabolic phenotypes in a population of Nicaraguan volunteers, indicating the need to improve the accuracy of phenotype prediction from genotypes.

PHARMACOGENOMICS JOURNAL (2021)

Article Biochemistry & Molecular Biology

Allele-specific alternative splicing and its functional genetic variants in human tissues

Kofi Amoah et al.

Summary: Alternative splicing is a RNA processing mechanism that affects most genes in human, and can be modulated by genetic variants. Utilizing GTEx data, the study of genetically modulated alternative splicing (GMAS) reveals that GMAS events are shared more frequently across tissues and individuals than expected by chance, indicating a genetically driven nature.

GENOME RESEARCH (2021)

Article Pharmacology & Pharmacy

Cytochrome P450 3A4 (CYP3A4) protein quantification using capillary western blot technology and total protein normalization

Joseph M. Collins et al.

Summary: The Western blot (WB) technique is commonly used for protein quantification in pharmacological and toxicological studies. Recent evidence suggests that internal standard house-keeping genes may change after drug treatments or in disease states, leading to errors in protein quantification using WB. Utilizing automated capillary-based WB technologies for total protein normalization provides a high throughput and robust approach for accurate protein quantification.

JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS (2021)

Article Cell Biology

Toward predicting CYP2D6-mediated variable drug response from CYP2D6 gene sequencing data

Maaike van der Lee et al.

Summary: The study introduces a proof-of-concept approach using continuous-scale assignments to predict CYP2D6 enzyme activity, showing potential for more accurate prediction of individual drug response compared to conventional *-allele approach. This model, trained with complete CYP2D6 gene sequences and tamoxifen metabolism data, explained a higher percentage of interindividual variability in enzyme activity and demonstrated advantages in predicting known and novel allele combinations.

SCIENCE TRANSLATIONAL MEDICINE (2021)

Review Pharmacology & Pharmacy

PharmVar GeneFocus: CYP2D6

Charity Nofziger et al.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2020)

Article Biotechnology & Applied Microbiology

Distribution and linkage disequilibrium of the enhancer SNP rs5758550 among Latin American populations: influence of continental ancestry

Anna Beatriz Ribeiro Elias et al.

PHARMACOGENETICS AND GENOMICS (2020)

Article Multidisciplinary Sciences

The GTEx Consortium atlas of genetic regulatory effects across human tissues

Francois Aguet et al.

SCIENCE (2020)

Article Pharmacology & Pharmacy

Examination of Metoprolol Pharmacokinetics and Pharmacodynamics Across CYP2D6 Genotype-Derived Activity Scores

Cameron D. Thomas et al.

CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY (2020)

Review Pharmacology & Pharmacy

Clinical Pharmacogenetics Implementation Consortium Guideline for Cytochrome P450 (CYP)2D6 Genotype and Atomoxetine Therapy

Jacob T. Brown et al.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2019)

Article Pharmacology & Pharmacy

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy

Matthew P. Goetz et al.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2018)

Article Pharmacology & Pharmacy

In vivo assessment of the metabolic activity of CYP2D6 diplotypes and alleles

Daniel L. Hertz et al.

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY (2015)

Article Biochemistry & Molecular Biology

Functional characterization of CYP2D6 enhancer polymorphisms

Danxin Wang et al.

HUMAN MOLECULAR GENETICS (2015)

Review Medicine, Research & Experimental

Mechanism of alternative splicing and its regulation

Yan Wang et al.

BIOMEDICAL REPORTS (2015)

Review Chemistry, Medicinal

Role of Protein-Protein Interactions in Cytochrome P450-Mediated Drug Metabolism and Toxicity

Sylvie E. Kandel et al.

CHEMICAL RESEARCH IN TOXICOLOGY (2014)

Article Pharmacology & Pharmacy

Functional Characterization of Wild-type and 49 CYP2D6 Allelic Variants for N-Desmethyltamoxifen 4-Hydroxylation Activity

Yuka Muroi et al.

DRUG METABOLISM AND PHARMACOKINETICS (2014)

Article Allergy

Pharmacogenetics: Implications of race and ethnicity on defining genetic profiles for personalized medicine

Victor E. Ortega et al.

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (2014)

Article Biochemistry & Molecular Biology

Effect of homomeric P450-P450 complexes on P450 function

James R. Reed et al.

BIOCHEMICAL JOURNAL (2012)

Article Multidisciplinary Sciences

An integrated map of genetic variation from 1,092 human genomes

David M. Altshuler et al.

NATURE (2012)

Article Genetics & Heredity

CYP2D6 genotype and debrisoquine hydroxylation phenotype in Cubans and Nicaraguans

A. LLerena et al.

PHARMACOGENOMICS JOURNAL (2012)

Article Pharmacology & Pharmacy

Assessment of Activity Levels for CYP2D6*1, CYP2D6*2, and CYP2D6*41 Genes by Population Pharmacokinetics of Dextromethorphan

K. Abduljalil et al.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2010)

Article Endocrinology & Metabolism

Identification of genetic variants of human cytochrome P450 2D6 with impaired mitochondrial targeting

Michelle Cook Sangar et al.

MOLECULAR GENETICS AND METABOLISM (2010)

Article Pharmacology & Pharmacy

The CYP2D6 activity score: Translating genotype information into a qualitative measure of phenotype

A. Gaedigk et al.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2008)

Letter Pharmacology & Pharmacy

The 2988G>A polymorphism affects splicing of a CYP2D6 minigene

Thomas Rau et al.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2006)

Article Biochemistry & Molecular Biology

Crystal structure of human cytochrome P450 2D6

P Rowland et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2006)

Article Medical Laboratory Technology

CYP2D6 genotyping by a multiplex primer extension reaction

J Sistonen et al.

CLINICAL CHEMISTRY (2005)

Article Pharmacology & Pharmacy

Tramadol as a new probe for cytochrome P450 2D6 phenotyping: A population study

RS Pedersen et al.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2005)

Article Gastroenterology & Hepatology

Stable expression of human cytochrome P450 2D6*10 in HepG2 cells

J Zhuge et al.

WORLD JOURNAL OF GASTROENTEROLOGY (2004)

Article Biotechnology & Applied Microbiology

Comprehensive analysis of the genetic factors determining expression and function of hepatic CYP2D6

UM Zanger et al.

PHARMACOGENETICS (2001)