Identification and characterization of a novel promoter variant in placental growth factor for neovascular age-related macular degeneration. (October 2019)

• Record Type: Journal Article
• Authors: Ma, Li; Ng, Tsz Kin; Chen, Haoyu; Brelén, Marten E.; Lai, Timothy Y.Y.; Ho, Mary; Tam, Pancy O.S.; Young, Alvin L.; Chen, Weiqi; Tham, Clement C.; Pang, Chi Pui; Chen, Li Jia
• Is Part Of: Experimental eye research. Volume 187(2019)
• Publication Date: 2019-10
• Subjects: Placental growth factor -- Age-related macular degeneration -- Promoter deletion variant -- Transcription; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2019.107748
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Purpose: Intronic variants in the placental growth factor (PGF) gene have been associated with neovascular age-related macular degeneration (AMD). This study is to discover and characterize rare variants in the PGF gene for neovascular AMD. Methods: The promoter region, coding sequences and splicing regions of the PGF gene were sequenced in a Hong Kong southern Chinese cohort of 235 neovascular AMD patients and 435 controls. A detected 18 base-pair deletion variant in the promoter region of PGF was analyzed in a Shantou southern Chinese cohort of 189 neovascular AMD patients and 846 controls. The transcription activity of this disease-associated promoter variant was determined in human ARPE-19 cells by promoter-luciferase analysis. Results: A novel 18-base-pair deletion mutation in the promoter region of PGF was identified in 3 (1.28%) patients and 1 (0.23%) control subject (OR = 5.61; 95% CI 0.58–54.26) in the Hong Kong cohort, and in 2 (1.06%) patients and 2 (0.24%) controls (OR = 4.51; 95% CI: 0.63–32.25) in the Shantou cohort. In the combined southern Chinese sample, this deletion had a significant association with neovascular AMD (P = 0.026; OR = 5.08, 95% CI: 1.21–21.36). The 18-base-pair deletion was predicted to alter the transcription factor binding sites in the PGF promoter, and higher luciferase expression was detected in ARPE-19 cells transfected with the deletion variant plasmid than those transfected with wild type plasmid (P = 0.0002). Conclusions: This study identified a rare, functional promoter variant in the PGF gene that increases PGF transcription activity and confers a 5-fold risk to neovascular AMD. Highlights: A novel 18 bp deletion in the promoter region of PGF was associated with AMD. The deletion variant increased transcription activity. The deletion variant may enrich our understanding of PGF in the pathogenesis of AMD.