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Susceptibility genes for gentamicin-induced vestibular dysfunction

Stephen M Roth1, Scott M Williams, Lan Jiang

  • 1Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD 20742-2611, USA. sroth1@umd.edu

Journal of Vestibular Research : Equilibrium & Orientation
|September 9, 2008
PubMed
Abstract

Insights

Gentamicin (GM) antibiotic use can cause vestibular ototoxicity. Genetic variations in NOS3, GSTZ1, and GSTP1 genes increase susceptibility to GM-induced balance dysfunction, particularly in carriers of specific risk alleles.

Area of Science:

  • Pharmacogenomics
  • Neuroscience
  • Genetics

Background:

  • Gentamicin (GM), an aminoglycoside antibiotic, can cause vestibular ototoxicity in approximately 5% of patients, leading to balance dysfunction.
  • Identifying genetic factors influencing susceptibility to GM-induced ototoxicity is crucial for personalized medicine and risk mitigation.

Purpose of the Study:

  • To identify specific gene polymorphisms associated with gentamicin-induced vestibular dysfunction.
  • To explore gene-gene interactions that may predict susceptibility to this adverse drug reaction.

Main Methods:

  • A case/control study design was employed, comparing patients with GM-induced vestibular dysfunction (cases) to healthy controls.
  • DNA from 137 cases and 126 controls was genotyped for 15 polymorphisms in 9 candidate genes, focusing on those involved in oxidative stress pathways.
  • Statistical analyses included single-gene association tests and multi-dimensionality reduction (MDR) to identify gene-gene interactions.

Main Results:

  • The NOS3 (ENOS) p.Glu298Asp polymorphism was significantly associated with GM-induced vestibular dysfunction (p ≤ 0.03).
  • A three-gene combination (NOS3, GSTZ1, GSTP1) using MDR analysis demonstrated the highest predictive accuracy (64%, p=0.009) for GM-induced vestibular dysfunction.

Conclusions:

  • Genetic variations in oxidative stress-related genes, specifically NOS3, GSTZ1, and GSTP1, are linked to increased susceptibility to gentamicin-induced vestibular ototoxicity.
  • Carriers of risk alleles in these genes may be at higher risk for developing balance dysfunction after GM administration.

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