CPIC Guideline: MT-RNR1 Genotyping to Prevent Aminoglycoside-Induced Hearing Loss
This Clinical Pharmacogenetics Implementation Consortium guideline recommends avoiding aminoglycosides in individuals carrying MT-RNR1 variants (m.1555A>G, m.1494C>T, m.1095T>C) that increase susceptibility to irreversible sensorineural hearing loss. The mitochondrial variants cause the 12S rRNA to resemble the bacterial 16S target, enhancing aminoglycoside binding. For clinical laboratories, the guideline supports implementing rapid MT-RNR1 genotyping, particularly in neonatal and intensive care settings where aminoglycosides are commonly used.
The original study
Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype.
- Authors
- McDermott JH, Wolf J, Hoshitsuki K, Huddart R, Caudle KE, Whirl-Carrillo M, et al.
- Journal
- Clinical pharmacology and therapeutics
- Type
- Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Practice Guideline
- PMID
- 34032273
Original abstract
Aminoglycosides are widely used antibiotics with notable side effects, such as nephrotoxicity, vestibulotoxicity, and sensorineural hearing loss (cochleotoxicity). MT-RNR1 is a gene that encodes the 12s rRNA subunit and is the mitochondrial homologue of the prokaryotic 16s rRNA. Some MT-RNR1 variants (i.e., m.1095T>C; m.1494C>T; m.1555A>G) more closely resemble the bacterial 16s rRNA subunit and result in increased risk of aminoglycoside-induced hearing loss. Use of aminoglycosides should be avoided in individuals with an MT-RNR1 variant associated with an increased risk of aminoglycoside-induced hearing loss unless the high risk of permanent hearing loss is outweighed by the severity of infection and safe or effective alternative therapies are not available. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of aminoglycosides based on MT-RNR1 genotype (updates at https://cpicpgx.org/guidelines/ and www.pharmgkb.org).