Mitochondrial DNA mutations associated with aminoglycoside induced ototoxicity.
Mitochondrial DNA mutations associated with aminoglycoside induced ototoxicity.
复制标题
与氨基糖甙类药物引起的耳毒性相关的线粒体 DNA 突变
DOI：
10.1016/j.joto.2017.02.001
复制
发表时间：
2017-03
影响因子：
1.9
通讯作者：
Guan MX
中科院分区：
文献类型：
--
作者：
Gao Z;Chen Y;Guan MX
氨基糖苷类 (AmAn) 因其对抗革兰氏阴性细菌感染的高效性而被广泛使用。然而，它们也会引起耳毒性听力损失，这已经影响了全世界数百万人。正如之前报道的，12S rRNA 基因中携带线粒体 DNA 突变（例如 m.1555A>G 和 m.1494C>T）的个体更容易出现 AmAn 诱导的耳毒性。这些突变导致人类线粒体核糖体更类似于细菌核糖体，并实现更强的氨基糖苷相互作用。因此，接触 AmAn 会诱发或加重这些人的听力损失。此外，在携带这些突变的家庭中观察到听力损失的严重程度和外显率存在很大差异。研究表明，这些线粒体突变是 AmAn 耳毒性遗传易感性的主要分子机制，尽管已知核修饰基因和线粒体单倍型可以调节表型表现。
Aminoglycosides (AmAn) are widely used for their great efficiency against gram-negative bacterial infections. However, they can also induce ototoxic hearing loss, which has affected millions of people around the world. As previously reported, individuals bearing mitochondrial DNA mutations in the 12S rRNA gene, such as m.1555A>G and m.1494C>T, are more prone to AmAn-induced ototoxicity. These mutations cause human mitochondrial ribosomes to more closely resemble bacterial ribosomes and enable a stronger aminoglycoside interaction. Consequently, exposure to AmAn can induce or worsen hearing loss in these individuals. Furthermore, a wide range of severity and penetrance of hearing loss was observed among families carrying these mutations. Studies have revealed that these mitochondria mutations are the primary molecular mechanism of genetic susceptibility to AmAn ototoxicity, though nuclear modifier genes and mitochondrial haplotypes are known to modulate the phenotypic manifestation.