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Related Concept Videos

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

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Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

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Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
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Principles of Pharmacogenetics: Types of Genetic Variants01:27

Principles of Pharmacogenetics: Types of Genetic Variants

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The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
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Pharmacogenetics and Pharmacogenomics: Overview01:29

Pharmacogenetics and Pharmacogenomics: Overview

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Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...
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Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

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Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
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Epigenetic Regulation01:37

Epigenetic Regulation

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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
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Methyl-binding DNA capture Sequencing for Patient Tissues
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Interethnic DNA methylation difference and its implications in pharmacoepigenetics.

Shih-Kai Chu1,2,3, Hsin-Chou Yang1,2,4,5,6,7

  • 1Bioinformatics Program, Taiwan International Graduate Program, Institute of Information Science, Academia Sinica, Taipei 115, Taiwan.

Epigenomics
|September 9, 2017
PubMed
Summary

This study reveals that DNA methylation patterns linked to ethnicity influence gene expression and drug metabolism across different tissues and cancers. Accounting for ethnicity is crucial for future pharmacoepigenetics research.

Keywords:
DNA methylationcancer epigeneticsepipharmacogenomicspopulation differentiation

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Area of Science:

  • Epigenetics
  • Pharmacogenomics
  • Cancer Biology

Background:

  • DNA methylation plays a critical role in gene regulation and cellular function.
  • Population differentiation in DNA methylation patterns may impact drug response and pharmacokinetics.
  • Understanding these variations is essential for personalized medicine.

Purpose of the Study:

  • To systematically investigate the impact of ethnicity-associated DNA methylation on treatment response and ADME (absorption, distribution, metabolism, and excretion).
  • To examine these effects across multiple tissue types and cancer types.
  • To explore population differentiation in DNA methylation patterns.

Main Methods:

  • Analysis of whole methylome and transcriptome data from primary tumor tissues and lymphoblastoid cell lines.
  • Comparison of methylation patterns between African and European ancestry populations.
  • Investigation across four cancer types: breast, colon, head & neck, and uterine corpus.

Main Results:

  • Ethnicity-associated CpG sites showed similar methylation patterns within populations but differed between tissue types (tumor vs. cell lines).
  • These sites may influence gene expression, affecting drug ADME.
  • Tumor-specific methylation and gene regulation patterns associated with ethnicity were observed.

Conclusions:

  • Ethnicity-associated DNA methylation patterns have functional implications for gene expression and drug metabolism.
  • These epigenetic variations exhibit tissue- and tumor-specific characteristics.
  • Future pharmacoepigenetics research must carefully consider ethnic population differences.