| First Author | Huang L | Year | 2016 |
| Journal | Nat Genet | Volume | 48 |
| Issue | 6 | Pages | 640-7 |
| PubMed ID | 27089177 | Mgi Jnum | J:260933 |
| Mgi Id | MGI:6152259 | Doi | 10.1038/ng.3546 |
| Citation | Huang L, et al. (2016) A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy. Nat Genet 48(6):640-7 |
| abstractText | 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 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. |
