Genetic Factors in Aminoglycoside Toxicity

@article{FischelGhodsian2005GeneticFI,
  title={Genetic Factors in Aminoglycoside Toxicity},
  author={Nathan Fischel‐Ghodsian},
  journal={Annals of the New York Academy of Sciences},
  year={2005},
  volume={884}
}
ABSTRACT: Ototoxicity is the major irreversible toxicity of aminoglycosides, and occurs both in a dose‐dependent and idiosyncratic fashion. The idiosyncratic pathway is presumably due to genetic predispositions, and in 1993 we identified an inherited mutation that predisposes to aminoglycoside ototoxicity, the A1555G mutation in the mitochondrial 12S ribosomal RNA gene. Seventeen‐33% of patients with aminoglycoside ototoxicity carry this mutation. 
Aminoglycoside toxicity in neonates: something to worry about?
TLDR
The animal and human evidence for aminoglycoside toxicity in neonates is reviewed including mechanisms, measurement and rates of toxicity; and differences between am inoglycosides and dosing regimens.
Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection
TLDR
These mechanisms of aminoglycosides' antimicrobial as well as ototoxic mechanisms are reviewed in regard to established and potential future targets of hair cell protection.
Mitochondrial DNA mutations associated with aminoglycoside induced ototoxicity
Pharmacogenomics of antimicrobial agents.
TLDR
Recent advances in the field of antimicrobial pharmacogenomics that potentially affect treatment efficacy and toxicity are examined, and challenges that exist between pharmacogenomic discovery and translation into clinical use are examined.
Genetics of aminoglycocide-induced and prelingual non-syndromic mitochondrial hearing impairment: A review
TLDR
The A1555G mutation in the 12S rRNA gene was frequently identified and was believed to target the mitochondrial ribosome in the cochlea resulting in abnormal RNA processing or decreased efficiency of translation leading to irreversible auditory dysfunction.
Pharmacodynamics and dosing of aminoglycosides.
  • J. Turnidge
  • Medicine
    Infectious disease clinics of North America
  • 2003
Aminoglycoside-induced ototoxicity.
  • E. Selimoğlu
  • Biology, Chemistry
    Current pharmaceutical design
  • 2007
TLDR
In this paper, incidence, predisposition, mechanism, and prevention of aminoglycoside-induced ototoxicity is discussed in the light of literature data.
Investigation of the genetic aetiology of aminoglycoside-induced hearing loss in South African populations
Thesis (MScMedSc (Biomedical Sciences. Molecular Biology and Human Genetics))--University of Stellenbosch, 2009.
Cisplatin and Aminoglycoside Antibiotics: Hearing Loss and Its Prevention
This review introduces the pathology of aminoglycoside antibiotic and the cisplatin chemotherapy classes of drugs, discusses oxidative stress in the inner ear as a primary trigger for cell damage,
Frequency of mitochondrial 12S ribosomal RNA variants in an adult cystic fibrosis population
TLDR
This work investigated the genetic predisposition to aminoglycoside ototoxicity in a typical unscreened North American cystic fibrosis population by screening for variants in mitochondrial 12S ribosomal RNA and noted several polymorphisms occurred at higher frequencies than expected and were associated with clinically significant cases of hearing loss.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 91 REFERENCES
Pharmacokinetics of aminoglycoside antibiotics in blood, inner-ear fluids and tissues and their relationship to ototoxicity.
  • C. Henley, J. Schacht
  • Biology, Chemistry
    Audiology : official organ of the International Society of Audiology
  • 1988
TLDR
This review critically evaluates the literature on aminoglycoside pharmacokinetics to answer the question how fluid and tissue levels of the drugs relate to the development of ototoxic and nephrotoxic side effects and suggests that studies of drug disposition at the cellular level after chronic aminglycoside treatment be conducted to establish whether a cell-specific uptake contributes to the selective toxicity of the aminoliccoside antibiotics.
Genetic aspects of antibiotic induced deafness: mitochondrial inheritance.
TLDR
Analysis of 36 pedigrees with a positive family history of aminoglycoside antibiotic induced deafness showed that the susceptibility to antibiotic ototoxicity was transmitted by females exclusively, indicating mitochondrial inheritance.
A biochemical basis for the inherited susceptibility to aminoglycoside ototoxicity.
TLDR
Results have provided the first direct evidence that the mitochondrial 12S rRNA carrying the A1555G mutation is the main target of aminoglycosides, and suggest that these antibiotics exert their detrimental effect through an alteration of mitochondrial protein synthesis, reducing the overall translation rate down to and below the minimal level required for normal cellular function.
A molecular basis for human hypersensitivity to aminoglycoside antibiotics.
TLDR
The frequency of a particular mitochondrial DNA polymorphism, 1555G, is associated nonrandomly with aminoglycoside-induced deafness in two Japanese pedigrees, bringing the frequency of this polymorphism to 5 occurrences in 5 pedigree of AGD.
Mitochondrial ribosomal RNA mutation associated with both antibiotic–induced and non–syndromic deafness
TLDR
This study offers the first description of a mitochondrial rRNA mutation leading to disease, the first cases of non–syndromic deafness caused by a mitochondrial DNA mutation and the first molecular genetic study of antibiotic–induced ototoxicity.
Susceptibility mutations in the mitochondrial small ribosomal RNA gene in aminoglycoside induced deafness.
TLDR
The description of these putative susceptibility mutations, in particular the heteroplasmic mutation around nt 961, provides further support for the important role of the mitochondrial 12S rRNA in genetic predisposition to aminoglycoside induced ototoxic deafness.
...
1
2
3
4
5
...