Genetic Factors in Aminoglycoside Toxicity

Ototoxicity is the major irreversible toxicity of aminoglycosides, and it occurs both in a dose-dependent and idiosyncratic fashion. The idiosyncratic pathway is presumably due to genetic predispositions, and an inherited mutation in the mitochondrial 12S ribosomal RNA gene that predisposes carriers to aminoglycoside ototoxicity was identified in 1993. Up to a third of patients with aminoglycoside ototoxicity carry this mutation. Two other mutations in the same mitochondrial gene affect a small minority of additional patients. Thus, the prevention of aminoglycoside-induced ototoxicity through family history and molecular diagnosis is possible in many cases. It is the challenge of genomic medicine to translate this more than a decade-old knowledge into clinical practice.