UCL Ear Institute, University College London, London, UK.
Neurobiol Aging. 2013 Aug;34(8):2077.e1-9. doi: 10.1016/j.neurobiolaging.2013.02.009. Epub 2013 Mar 26.
Since estrogen is thought to protect pre-menopausal women from age-related hearing loss, we investigated whether variation in estrogen-signalling genes is linked to hearing status in the 1958 British Birth Cohort. This analysis implicated the estrogen-related receptor gamma (ESRRG) gene in determining adult hearing function and was investigated further in a total of 6134 individuals in 3 independent cohorts: (i) the 1958 British Birth Cohort; (ii) a London ARHL case-control cohort; and (iii) a cohort from isolated populations of Italy and Silk Road countries. Evidence of an association between the minor allele of single nucleotide polymorphism (SNP) rs2818964 and hearing status was found in females, but not in males in 2 of these cohorts: p = 0.0058 (London ARHL) and p = 0.0065 (Carlantino, Italy). Furthermore, assessment of hearing in Esrrg knock-out mice revealed a mild 25-dB hearing loss at 5 weeks of age. At 12 weeks, average hearing thresholds in female mice((-/-)) were 15 dB worse than in males((-/-)). Together these data indicate ESRRG plays a role in maintenance of hearing in both humans and mice.
由于雌激素被认为可以保护绝经前女性免受与年龄相关的听力损失，我们调查了雌激素信号基因的变异是否与 1958 年英国出生队列中的听力状况有关。这项分析表明，雌激素相关受体γ（ESRRG）基因决定了成人的听力功能，并在三个独立队列中的总共 6134 个人中进行了进一步研究：（i）1958 年英国出生队列；（ii）伦敦 ARHL 病例对照队列；（iii）来自意大利和丝绸之路国家的隔离人群队列。在这两个队列中的女性中发现了单核苷酸多态性（SNP）rs2818964 的次要等位基因与听力状况之间存在关联，但在男性中则没有：p = 0.0058（伦敦 ARHL）和 p = 0.0065（意大利卡尔兰蒂诺）。此外，对 Esrrg 敲除小鼠的听力评估显示，在 5 周龄时出现轻微的 25dB 听力损失。在 12 周时，雌性小鼠（（-/-））的平均听力阈值比雄性小鼠（（-/-））差 15dB。这些数据表明，ESRRG 在人类和小鼠的听力维持中都发挥作用。
