Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester, UK.
Clin Pharmacol Ther. 2022 Feb;111(2):366-372. doi: 10.1002/cpt.2309. Epub 2021 Jun 20.
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).
氨基糖苷类抗生素是一类具有显著副作用的抗生素，如肾毒性、前庭毒性和感觉神经性听力损失（耳蜗毒性）。MT-RNR1 是一个编码 12s rRNA 亚基的基因，是原核生物 16s rRNA 的线粒体同源物。一些 MT-RNR1 变体（即 m.1095T>C；m.1494C>T；m.1555A>G）更类似于细菌 16s rRNA 亚基，导致氨基糖苷类药物诱导性听力损失的风险增加。除非感染的严重程度超过永久性听力损失的高风险，并且没有安全或有效的替代疗法可用，否则应避免在携带与氨基糖苷类药物诱导性听力损失风险增加相关的 MT-RNR1 变体的个体中使用氨基糖苷类药物。我们总结了支持这种关联的文献证据，并根据 MT-RNR1 基因型提供了氨基糖苷类药物使用的治疗建议（更新于 https://cpicpgx.org/guidelines/ 和 www.pharmgkb.org）。
