Identification of PGF as a New Gene for Neovascular Age-Related Macular Degeneration in a Chinese Population

PURPOSE. To determine the associations of the VEGFA, VEGFB, and placental growth factor (PGF) genes with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS. Seven single-nucleotide polymorphisms (SNPs) in VEGFA, three SNPs in VEGFB, and five SNPs in PGF were genotyped in 1722 unrelated Chinese participants, including a Hong Kong cohort of 214 nAMD patients, 236 PCV patients, and 365 controls, and an independent Shantou cohort of 189 nAMD patients, 187 PCV patients, and 531 controls, using TaqMan genotyping assays. RESULTS. Placental growth factor SNPs rs2268615 (G allele, P = 0.0047; odds ratio [OR] = 1.54, 95% confidence interval [CI], 1.14-2.08) and rs2268614 (G allele, P = 0.015; OR = 1.46, 95% CI, 1.07-1.97) were associated with nAMD. A significant omnibus haplotype association with nAMD was detected for a two-SNP window containing rs2268615 and rs2268614, with a haplotype G-G conferring a 1.54-fold increased risk (P = 0.0042) in the Hong Kong cohort and a 1.42-fold risk (P = 0.012) in the Shantou cohort. Pooling of the Hong Kong and Shantou data enhanced the association of nAMD with rs2268615 (P = 0.0022; OR = 1.38, 95% CI, 1.12-1.69; I2 = 0%), rs2268614 (P = 0.0067; OR = 1.33, 95% CI, 1.08-1.63; I2 = 0%), and the G-G haplotype (P = 0.0013; OR = 1.46, 95% CI, 1.16-1.84; I2 = 0%). In contrast, the PGF SNPs and haplotype were not associated with PCV. Our results also revealed no association of SNPs in VEGFA and VEGFB with nAMD or PCV. CONCLUSION. Placental growth factor is a susceptibility gene for nAMD in a Chinese population, providing new evidence to support a biological role of PGF in choroidal neovascularization.