| Literature DB >> 25872646 |
Lv-Zhen Huang1, Ying-Jie Li2, Xue-Feng Xie3, Jing-Jing Zhang1, Ching-Yu Cheng4, Kenji Yamashiro5, Li-Jia Chen6, Xiao-Yun Ma7, Chui Ming G Cheung8, Yu-Sheng Wang9, Chun-Fang Zhang10, Yu-Jing Bai1, Jing Hou1, Xiao-Li Chen1, Yun Qi1, Shan-Shan Li1, Yao-Yao Sun1, Jun-Pu Mei3, Yong Cheng1, Wen-Zhen Yu1, Xiong-Bing Hu11, Feng-Feng Zhuang11, Lei Fan12, Yi Lu13, Xing-Huai Sun13, Xiang-Jia Zhu13, De-Fen Shen14, Chi-Chao Chan14, Ming-Wei Zhao1, Nagahisa Yoshimura5, Chi Pui Pang6, Tien Yin Wong4, Chiea Chuen Khor15, Kang Zhang16, Peng Zhou17, Xiao-Xin Li1.
Abstract
Age-related macular degeneration (AMD) is a leading cause of irreversible central blindness among the elderly worldwide. We use exome sequencing to analyse nonsynonymous single-nucleotide variants (SNVs) across the whole genome of 216 neovascular AMD cases and 1,553 controls. As a follow-up validation, we evaluate 3,772 neovascular AMD cases and 6,942 controls from five independent cohorts in the East Asian population. Here we show strong evidence of an association at a novel, missense SNV, rs7739323, which is located in the ubiquitin protein ligase E3D (UBE3D) gene (Pmeta=1.46 × 10(-9), odds ratio (OR)=0.74, 95% confidence interval (CI): 0.63-0.88). Furthermore, ablation of the UBE3D protein lead to an abnormal amount of pigment granules deposited in retinal pigment epithelium microvilli area and an abnormal response on electroretinography (ERG) in UBE3D(+/-) heterozygous mice. Our findings indicate that the ubiquitin-proteasome system may play a role in the pathogenesis of neovascular AMD.Entities:
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Year: 2015 PMID： 25872646 DOI： 10.1038/ncomms7687
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919