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

Publication ,  Journal Article
Huang, L; Zhang, H; Cheng, C-Y; Wen, F; Tam, POS; Zhao, P; Chen, H; Li, Z; Chen, L; Tai, Z; Yamashiro, K; Deng, S; Zhu, X; Chen, W; Cai, L ...
Published in: Nat Genet
June 2016
Published version (DOI) Link to item

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.

Duke Scholars

Tien Yin Wong
Author Tien Yin Wong Ophthalmology
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Published In

Nat Genet

DOI

10.1038/ng.3546

EISSN

1546-1718

Publication Date

June 2016

Volume

48

Issue

6

Start / End Page

640 / 647

Location

United States

Related Subject Headings

  • Wet Macular Degeneration
  • Subcellular Fractions
  • Polymorphism, Single Nucleotide
  • Mutation, Missense
  • Humans
  • Guanine Nucleotide Exchange Factors
  • Gene Expression Profiling
  • Ethnicity
  • Endothelium, Vascular
  • Developmental Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Huang, L., Zhang, H., Cheng, C.-Y., Wen, F., Tam, P. O. S., Zhao, P., … Yang, Z. (2016). A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy. Nat Genet, 48(6), 640–647. https://doi.org/10.1038/ng.3546
Huang, Lulin, Houbin Zhang, Ching-Yu Cheng, Feng Wen, Pancy O. S. Tam, Peiquan Zhao, Haoyu Chen, et al. “A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy.” Nat Genet 48, no. 6 (June 2016): 640–47. https://doi.org/10.1038/ng.3546.
Huang L, Zhang H, Cheng C-Y, Wen F, Tam POS, Zhao P, et al. A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy. Nat Genet. 2016 Jun;48(6):640–7.
Huang, Lulin, et al. “A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy.” Nat Genet, vol. 48, no. 6, June 2016, pp. 640–47. Pubmed, doi:10.1038/ng.3546.
Huang L, Zhang H, Cheng C-Y, Wen F, Tam POS, Zhao P, Chen H, Li Z, Chen L, Tai Z, Yamashiro K, Deng S, Zhu X, Chen W, Cai L, Lu F, Li Y, Cheung C-MG, Shi Y, Miyake M, Lin Y, Gong B, Liu X, Sim K-S, Yang J, Mori K, Zhang X, Cackett PD, Tsujikawa M, Nishida K, Hao F, Ma S, Lin H, Cheng J, Fei P, Lai TYY, Tang S, Laude A, Inoue S, Yeo IY, Sakurada Y, Zhou Y, Iijima H, Honda S, Lei C, Zhang L, Zheng H, Jiang D, Wong T-Y, Khor C-C, Pang C-P, Yoshimura N, Yang Z. A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy. Nat Genet. 2016 Jun;48(6):640–647.

Published In

Nat Genet

DOI

10.1038/ng.3546

EISSN

1546-1718

Publication Date

June 2016

Volume

48

Issue

6

Start / End Page

640 / 647

Location

United States

Related Subject Headings

  • Wet Macular Degeneration
  • Subcellular Fractions
  • Polymorphism, Single Nucleotide
  • Mutation, Missense
  • Humans
  • Guanine Nucleotide Exchange Factors
  • Gene Expression Profiling
  • Ethnicity
  • Endothelium, Vascular
  • Developmental Biology