Format

Send to

Choose Destination
Nat Genet. 2016 Jun;48(6):640-7. doi: 10.1038/ng.3546. Epub 2016 Apr 18.

A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy.

Huang L1,2,3,4, Zhang H1,4, Cheng CY5,6,7, Wen F8, Tam PO8, Zhao P9, Chen H10, Li Z5,6,11, Chen L12, Tai Z1,2,3,4, Yamashiro K13, Deng S1,4, Zhu X1,4, Chen W10, Cai L1, Lu F1, Li Y1, Cheung CM5,6, Shi Y1,4, Miyake M13, Lin Y1,4, Gong B1, Liu X1, Sim KS5,8,11, Yang J1, Mori K14, Zhang X8, Cackett PD5,15, Tsujikawa M16, Nishida K16, Hao F1, Ma S1, Lin H1, Cheng J1, Fei P9, Lai TY12, Tang S8, Laude A17, Inoue S18, Yeo IY5,7, Sakurada Y19, Zhou Y1, Iijima H20, Honda S19, Lei C21, Zhang L1,4, Zheng H1, Jiang D1, Zhu X1, Wong TY5,6,7, Khor CC5,6,11, Pang CP12, Yoshimura N13, Yang Z1,2,3,4.

Author information

1
Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
2
Institute of Chengdu Biology, Chinese Academy of Sciences, Chengdu, China.
3
Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, China.
4
Center of Information in Biomedicine, University of Electronic Science and Technology of China, Chengdu, China.
5
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
6
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
7
Duke-National University of Singapore Graduate Medical School, Singapore.
8
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
9
Department of Ophthalmology, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, China.
10
Joint Shantou International Eye Center, Shantou University and Chinese University of Hong Kong, Shantou, China.
11
Department of Human Genetics, Genome Institute of Singapore, Singapore.
12
Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong, China.
13
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
14
Department of Ophthalmology, Saitama Medical University, Iruma, Japan.
15
Princess Alexandra Eye Pavilion, Edinburgh, UK.
16
Department of Ophthalmology, Osaka University Medical School, Osaka, Japan.
17
National Health care Group Eye Institute, Tan Tock Seng Hospital, Singapore.
18
Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
19
Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan.
20
Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
21
Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.

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.

PMID:
27089177
DOI:
10.1038/ng.3546
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center