IMHE OpenIR
A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy
Huang, Lulin1,2,3,4,5; Zhang, Houbin1,2,5; Cheng, Ching-Yu6,7,8; Wen, Feng9; Tam, Pancy O. S.9; Zhao, Peiquan10; Chen, Haoyu11,12; Li, Zheng6,7,13; Chen, Lijia14; Tai, Zhengfu1,2,3,4,5; Yamashiro, Kenji15; Deng, Shaoping16; Zhu, Xianjun1,2,5; Chen, Weiqi11,12; Cai, Li1,2; Lu, Fang1,2; Li, Yuanfeng1,2; Cheung, Chui-Ming G.6,7; Shi, Yi1,2,5; Miyake, Masahiro15; Lin, Yin1,2,5; Gong, Bo1,2; Liu, Xiaoqi1,2; Sim, Kar-Seng13; Yang, Jiyun1,2; Mori, Keisuke16; Zhang, Xiongzhe9; Cackett, Peter D.6,17; Tsujikawa, Motokazu18; Nishida, Kohji18; Hao, Fang1,2; Ma, Shi1,2; Lin, He1,2; Cheng, Jing1,2; Fei, Ping10; Lai, Timothy Y. Y.14; Tang, Sibo9; Laude, Augustinus19; Inoue, Satoshi20; Yeo, Ian Y.6,8; Sakurada, Yoichi21; Zhou, Yu1,2; Iijima, Hiroyuki22; Honda, Shigeru21; Lei, Chuntao23,24; Zhang, Lin1,2,5; Zheng, Hong1,2; Jiang, Dan1,2; Zhu, Xiong1,2; Wong, Tien-Ying6,7,8; Khor, Chiea-Chuen6,7,13; Pang, Chi-Pui14; Yoshimura, Nagahisa15; Yang, Zhenglin1,2,3,4,5
2016-06-01
Source PublicationNATURE GENETICS
ISSN1061-4036
Volume48Issue:6Pages:640-+
AbstractPolypoidal 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 x 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.
DOI10.1038/ng.3546
WOS KeywordGENOME-WIDE ASSOCIATION ; CENTRAL SEROUS CHORIORETINOPATHY ; FACTOR-H GENE ; MACULAR DEGENERATION SUBTYPES ; NUCLEOTIDE EXCHANGE FACTOR ; COMPLEMENT COMPONENT 2 ; OXIDIZED PHOSPHOLIPIDS ; OXIDATIVE STRESS ; JAPANESE POPULATION ; DENSITY-LIPOPROTEIN
Language英语
Funding ProjectNational Natural Science Foundation of China[81170883] ; National Natural Science Foundation of China[81430008] ; National Natural Science Foundation of China[81200723] ; National Natural Science Foundation of China[81300802] ; National Natural Science Foundation of China[81170882] ; National Natural Science Foundation of China[81371030] ; National Natural Science Foundation of China[81271005] ; Department of Science and Technology of Sichuan Province, China[2014SZ0169] ; Department of Science and Technology of Sichuan Province, China[2015SZ0052] ; Department of Science and Technology of Sichuan Province, China[2015SZ0060] ; Department of Science and Technology of Sichuan Province, China[2016HH00X] ; Department of Science and Technology of Sichuan Province, China[2015JQO057] ; Department of Science and Technology of Sichuan Province, China[2014HH0009] ; Department of Science and Technology of Sichuan Province, China[2014JZ0004] ; General Research Fund, Hong Kong[467708] ; General Research Fund, Hong Kong[468810] ; National Medical Research Council, Singapore[NMRC/TCR/002-SERI/2008] ; National Medical Research Council, Singapore[R626/47/2008TCR] ; National Medical Research Council, Singapore[CSA R613/34/2008] ; National Medical Research Council, Singapore[NMRC 0796/2003] ; National Medical Research Council, Singapore[STaR/0003/2008] ; National Research Foundation of Singapore, Biomedical Research Council, Singapore[BMRC 09/1/35/19/616] ; National Research Foundation of Singapore, Biomedical Research Council, Singapore[08/1/35/19/550] ; National Research Foundation of Singapore, Biomedical Research Council, Singapore[10/1/35/19/675] ; Genome Institute of Singapore[GIS/12-AR2105] ; National Medical Research Council (NMRC)[0796/2003] ; National Medical Research Council (NMRC)[IRG07nov013] ; National Medical Research Council (NMRC)[IRG09nov014] ; National Medical Research Council (NMRC)[NMRC 1176/2008] ; National Medical Research Council (NMRC)[NIG/1003/2009] ; National Medical Research Council (NMRC)[CG/SERI/2010] ; National Medical Research Council (NMRC)[CSA/033/2012] ; Biomedical Research Council in Singapore[BMRC 08/1/35/19/550] ; Biomedical Research Council in Singapore[09/1/35/19/616] ; Biomedical Research Council in Singapore[10/1/35/19/671] ; Bright Focus Foundation, USA[M2011068]
WOS Research AreaGenetics & Heredity
WOS SubjectGenetics & Heredity
WOS IDWOS:000376744200011
Funding OrganizationNational Natural Science Foundation of China ; Department of Science and Technology of Sichuan Province, China ; General Research Fund, Hong Kong ; National Medical Research Council, Singapore ; National Research Foundation of Singapore, Biomedical Research Council, Singapore ; Genome Institute of Singapore ; National Medical Research Council (NMRC) ; Biomedical Research Council in Singapore ; Bright Focus Foundation, USA
PublisherNATURE PUBLISHING GROUP
Citation statistics
Document Type期刊论文
Identifierhttp://ir.imde.ac.cn/handle/131551/26219
Collection中国科学院水利部成都山地灾害与环境研究所
Corresponding AuthorYang, Zhenglin
Affiliation1.Univ Elect Sci & Technol China, Sch Med, Sichuan Acad Med Sci, Key Lab Human Dis Gene Study, Chengdu 610054, Peoples R China
2.Univ Elect Sci & Technol China, Sch Med, Sichuan Prov Peoples Hosp, Chengdu 610054, Peoples R China
3.Chinese Acad Sci, Inst Chengdu Biol, Chengdu, Peoples R China
4.Chinese Acad Sci, Sichuan Translat Med Hosp, Chengdu, Peoples R China
5.Univ Elect Sci & Technol China, Ctr Informat Biomed, Chengdu 610054, Peoples R China
6.Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore
7.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117595, Singapore
8.Duke Natl Univ Singapore Grad Med Sch, Singapore, Singapore
9.Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Peoples R China
10.Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Ophthalmol, Shanghai, Peoples R China
11.Shantou Univ, Joint Shantou Int Eye Ctr, Shantou, Peoples R China
12.Chinese Univ Hong Kong, Shantou, Peoples R China
13.Genome Inst Singapore, Dept Human Genet, Singapore, Singapore
14.Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China
15.Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kyoto, Japan
16.Saitama Med Univ, Dept Ophthalmol, Iruma, Saitama, Japan
17.Princess Alexandra Eye Pavil, Edinburgh, Midlothian, Scotland
18.Osaka Univ, Sch Med, Dept Ophthalmol, Osaka, Japan
19.Tan Tock Seng Hosp, Natl Hlth Care Grp Eye Inst, Singapore, Singapore
20.Saitama Med Univ, Res Ctr Genom Med, Div Gene Regulat & Signal Transduct, Saitama, Japan
21.Kobe Univ, Grad Sch Med, Div Ophthalmol, Dept Surg, Kobe, Hyogo 657, Japan
22.Univ Yamanashi, Fac Med, Dept Ophthalmol, Yamanashi, Japan
23.Sichuan Acad Med Sci, Dept Ophthalmol, Chengdu, Peoples R China
24.Sichuan Prov Peoples Hosp, Chengdu, Peoples R China
Recommended Citation
GB/T 7714
Huang, Lulin,Zhang, Houbin,Cheng, Ching-Yu,et al. A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy[J]. NATURE GENETICS,2016,48(6):640-+.
APA Huang, Lulin.,Zhang, Houbin.,Cheng, Ching-Yu.,Wen, Feng.,Tam, Pancy O. S..,...&Yang, Zhenglin.(2016).A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy.NATURE GENETICS,48(6),640-+.
MLA Huang, Lulin,et al."A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy".NATURE GENETICS 48.6(2016):640-+.
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