A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy
Publication in refereed journal


摘要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.
著者Huang LL, Zhang HB, Cheng CY, Wen F, Tam POS, Zhao PQ, Chen HY, Li Z, Chen LJ, Tai ZF, Yamashiro K, Deng SP, Zhu XJ, Chen WQ, Cai L, Lu F, Li YF, Cheung CMG, Shi Y, Miyake M, Lin Y, Gong B, Liu XQ, Sim KS, Yang JY, Mori K, Zhang XZ, Cackett PD, Tsujikawa M, Nishida K, Hao F, Ma S, Lin H, Cheng J, Fei P, Lai TYY, Tang SB, Laude A, Inoue S, Yeo IY, Sakurada Y, Zhou Y, Iijima H, Honda S, Lei CT, Zhang L, Zheng H, Jiang D, Zhu X, Wong TY, Khor CC, Pang CP, Yoshimura N, Yang ZL
期刊名稱Nature Genetics
頁次640 - +
Web of Science 學科類別Genetics & Heredity

上次更新時間 2021-27-01 於 00:54