| Literature DB >> 27089177 |
Lulin Huang1,2,3,4, Houbin Zhang1,4, Ching-Yu Cheng5,6,7, Feng Wen8, Pancy O S Tam8, Peiquan Zhao9, Haoyu Chen10, Zheng Li5,6,11, Lijia Chen12, Zhengfu Tai1,2,3,4, Kenji Yamashiro13, Shaoping Deng1,4, Xianjun Zhu1,4, Weiqi Chen10, Li Cai1, Fang Lu1, Yuanfeng Li1, Chui-Ming G Cheung5,6, Yi Shi1,4, Masahiro Miyake13, Yin Lin1,4, Bo Gong1, Xiaoqi Liu1, Kar-Seng Sim5,8,11, Jiyun Yang1, Keisuke Mori14, Xiongzhe Zhang8, Peter D Cackett5,15, Motokazu Tsujikawa16, Kohji Nishida16, Fang Hao1, Shi Ma1, He Lin1, Jing Cheng1, Ping Fei9, Timothy Y Y Lai12, Sibo Tang8, Augustinus Laude17, Satoshi Inoue18, Ian Y Yeo5,7, Yoichi Sakurada19, Yu Zhou1, Hiroyuki Iijima20, Shigeru Honda19, Chuntao Lei21, Lin Zhang1,4, Hong Zheng1, Dan Jiang1, Xiong Zhu1, Tien-Ying Wong5,6,7, Chiea-Chuen Khor5,6,11, Chi-Pui Pang12, Nagahisa Yoshimura13, Zhenglin Yang1,2,3,4.
Abstract
Polypoidal choroidal vasculopathy (PCV), a subtype of 'wet' age-related macular degeneration (AMD), constitutes up to 55% of cases of wet AMD in Asian patients. In contrast to the choroidal neovascularization (CNV) subtype, the genetic risk factors for PCV are relatively unknown. Exome sequencing analysis of a Han Chinese cohort followed by replication in four independent cohorts identified a rare c.986A>G (p.Lys329Arg) variant in the FGD6 gene as significantly associated with PCV (P = 2.19 × 10(-16), odds ratio (OR) = 2.12) but not with CNV (P = 0.26, OR = 1.13). The intracellular localization of FGD6-Arg329 is distinct from that of FGD6-Lys329. In vitro, FGD6 could regulate proangiogenic activity, and oxidized phospholipids increased expression of FGD6. FGD6-Arg329 promoted more abnormal vessel development in the mouse retina than FGD6-Lys329. Collectively, our data suggest that oxidized phospholipids and FGD6-Arg329 might act synergistically to increase susceptibility to PCV.Entities:
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Year: 2016 PMID： 27089177 DOI： 10.1038/ng.3546
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330