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The Association Between Promoter Tandem Repeat Polymorphism (pVNTR) and CYP2C9 Gene Expression in Human Liver Samples

  • 0Department of Pharmacotherapy and Translational Research, College of Pharmacy, Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, FL 32610, USA.
Genes +

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February 26, 2025

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February 26, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

A novel CYP2C9 promoter polymorphism, pVNTR-S, is linked to reduced CYP2C9 expression and drug metabolism. This finding helps explain previously unexplained variability in CYP2C9 activity, independent of known genetic markers.

Area Of Science

  • Pharmacogenomics
  • Drug Metabolism
  • Genetic Polymorphisms

Background

  • CYP2C9 is crucial for metabolizing 20% of drugs.
  • Known CYP2C9 single-nucleotide polymorphisms (SNPs) explain only part of expression variability.
  • A promoter variable number tandem repeat (pVNTR) polymorphism was previously identified.

Purpose Of The Study

  • To clarify the association between the CYP2C9 promoter pVNTR-S and CYP2C9 mRNA expression.
  • To assess the impact of pVNTR-S on CYP2C9 expression independently of known biomarkers.
  • To investigate the role of pVNTR-S in explaining unexplained CYP2C9 expression variability.

Main Methods

  • Gene expression measured by real-time quantitative PCR (qPCR).
  • Single-nucleotide polymorphisms (SNPs) and pVNTRs genotyped using SNapShot assays and fragment analysis.
  • Associations analyzed using multiple linear regression.

Main Results

  • The pVNTR-S was significantly associated with lower CYP2C9 expression (34% reduction, p=0.032) in human liver samples (n=247).
  • This association was independent of known CYP2C9 biomarkers (*2, *3, *8, rs12777823).
  • pVNTR-S may explain additional variability in CYP2C9 expression.

Conclusions

  • The CYP2C9 promoter pVNTR-S polymorphism directly impacts CYP2C9 mRNA expression.
  • pVNTR-S is a novel, independent predictor of reduced CYP2C9 activity.
  • This finding contributes to understanding inter-individual variability in drug response.

Keywords:

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