A few inherited variants in MT-RNR1, a mitochondrial gene, make the inner ear unusually sensitive to aminoglycoside antibiotics such as gentamicin; the most studied is m.1555A>G. In a carrier, standard doses, sometimes a single one, can cause permanent sensorineural hearing loss. The variants pass down the maternal line, and a genetic test can find them before treatment.

Why it matters for tinnitus

Aminoglycoside hearing loss is usually irreversible, and ototoxic medications explains why the tinnitus that comes with it is frequently permanent too. The UK regulator, the MHRA, notes deafness in carriers whose blood levels stayed within the recommended range, so blood-level monitoring, the usual safeguard, cannot be relied on to protect a carrier. A test for these variants predicts a reaction to a drug, not tinnitus: the genetics of tinnitus itself involve many genes of small effect.

What the evidence says

  • Discovery (family study). In 1993, four families with maternally inherited deafness, three of them linked to aminoglycosides, were found to share m.1555A>G.
  • Mechanism (guideline). The variants make a mitochondrial ribosomal RNA more like its bacterial counterpart, the aminoglycoside target, says the 2022 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline.
  • Strength (systematic review, guideline). A 2024 systematic review of 31 studies found the strongest evidence for m.1555A>G and m.1494C>T, with hearing loss after exposure reported in up to 100% and 40% of carriers respectively, though study quality was limited. CPIC rates the evidence high for both and moderate for m.1095T>C, and strongly recommends that carriers avoid aminoglycosides unless infection severity outweighs the hearing risk and no safe or effective alternative exists.
  • Prevalence (population cohort). In the British 1958 birth cohort, 19 of 7,350 people carried m.1555A>G, about 1 in 385; their hearing at 44 to 45 did not differ significantly from non-carriers', though drug exposure was not recorded.
  • Rapid testing (implementation study, NICE). In two UK neonatal intensive care units, a bedside test genotyped m.1555A>G in 26 minutes; among 751 babies, all three carriers found avoided aminoglycosides, and time to antibiotics matched previous practice. NICE's 2023 early value assessment says the Genedrive MT-RNR1 ID Kit can be used while more evidence is generated, with positive results confirmed by laboratory testing.
  • Tinnitus (screening, questionnaire and case studies). The tinnitus evidence is thin: PubMed returns three records for these variants and tinnitus. In a Japanese genetic screening study, 13 of 16 m.1555A>G carriers with hearing loss had tinnitus; in a Polish questionnaire study, 1 of 7 did. Neither reported aminoglycoside exposure. One case report found a neighbouring variant, m.1556C>T, in a patient with 45 years of tinnitus after streptomycin.

What this means for you

  • If you carry one of these variants, or relatives lost hearing after an aminoglycoside, tell your doctor or pharmacist before taking one, as the MHRA advises. A 2026 UK guideline (CERSI-PGx) suggests recording a carrier result as a drug reaction in your allergy record.
  • Your result also concerns your mother, siblings, maternal aunts, uncles and grandmother, and, if you are a woman, all your children.
  • The MHRA and the UK guideline both say testing should not delay urgent treatment, such as for suspected sepsis, but support it where treatment can be planned. In England the laboratory test is nationally commissioned.
  • A negative result does not eliminate the risk, and a carrier's uneventful earlier course does not remove it for later doses. The MHRA recommends hearing checks before, during and after treatment for all patients: see ototoxicity monitoring.
  • The UK guideline judges that vaccination's benefits far outweigh any theoretical risk from trace aminoglycosides in some vaccines.
  • CPIC calls aminoglycoside ear drops relatively contraindicated in anyone with a perforated eardrum, and says they are not known to be linked to these variants.
  • Tell the treating team promptly about new ringing, hearing loss or unsteadiness during or after a course. Hearing that drops over hours to three days needs same-day assessment.

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