Genetic susceptibility to aminoglycoside ototoxicity

Aminoglycosides are a well-known clinically relevant antibiotic family used to treat bacterial infections in humans and animals and can produce toxic side effects. Aminoglycoside-induced hearing loss (HL) has been shown to have a genetic susceptibility. Mitochondrial DNA mutations have been implicated in inherited and acquired hearing impairment.

Literature review of genetic mutations associated with aminoglycoside-induced ototoxicity.

PubMed was accessed from 1993 to 2017 using the search terms "aminoglycoside, genetic, ototoxicity, hearing loss". Exclusion criteria consisted of a literature in a language other than English, uncompleted or ongoing studies, literature with non-hearing related diseases, literature on ototoxicity due to cisplatin/carboplatin based chemotherapy, literature on ototoxicity from loop diuretics, animal studies, literature studying oto-protective agents, and literature without documented aminoglycoside exposure.

108 articles were originally identified, and 25 articles were included in our review. Mitochondrial 12S rRNA mutations were identified in all 25 studies in a total of 220 patients. Eight studies identified A1555G mutation as primary genetic factor underlying HL in cases of aminoglycoside-induced ototoxicity. The next most common mutation identified was C1494T.

Mitochondrial 12s rRNA mutation A1555G was present in American, Chinese, Arab-Israeli, Spanish and Mongolian ethnicities. All mutations leading to aminoglycoside ototoxicity were mitochondrial mutations.

Consideration of preexisting genetic defects may be valuable in treatments involving aminoglycosides. In particular populations such as those of Chinese origin, clinicians should continue to consider the increased susceptibility to aminoglycosides.