Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss.

Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss.
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DOI:
10.1038/ng.3217
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发表时间:
2015-03
期刊:
影响因子:
30.8
通讯作者:
Yang, Jun J.
Yang, Jun J.
中科院分区:
生物学1区
文献类型:
--
作者:
Xu, Heng;Robinson, Giles W.;Huang, Jie;Lim, Joshua Yew-Suang;Zhang, Hui;Bass, Johnnie K.;Broniscer, Alberto;Chintagumpala, Murali;Bartels, Ute;Gururangan, Sri;Hassall, Tim;Fisher, Michael;Cohn, Richard;Yamashita, Tetsuji;Teitz, Tal;Zuo, Jian;Onar-Thomas, Arzu;Gajjar, Amar;Stewart, Clinton F.;Yang, Jun J.

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采用全基因组关联研究方法,我们在 238 名新诊断脑肿瘤的儿童中发现了与顺铂耳毒性相关的 ACYP2 遗传变异(rs1872328,P = 3.9×10-8,风险比 = 4.5),并在 68 名接受类似治疗的儿童中独立复制。 ACYP2 风险变异使患者极易出现听力急剧下降,并且与耳毒性严重程度相关。这些结果表明铂制剂的耳毒性作用具有新颖的生物学意义。
Taking a genome-wide association study approach, we identified inherited genetic variations in ACYP2 associated with cisplatin ototoxicity (rs1872328, P = 3.9×10-8, hazard ratio = 4.5) in 238 children with newly-diagnosed brain tumors, with independent replication in 68 similarly treated children. ACYP2 risk variant strongly predisposed patients to precipitous hearing loss and was related to ototoxicity severity. These results point to novel biology of ototoxic effects of platinum agents.
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