VEGF Polymorphisms Are Associated with Severity of Diabetic Retinopathy

• Published in: Investigative ophthalmology & visual science 2008-08, Vol.49 (8), p.3611-3616
• Main Authors: Churchill, Amanda J, Carter, James G, Ramsden, Conor, Turner, Steven J, Yeung, Anna, Brenchley, Paul E. C, Ray, David W
• Format: Article
• Language: English
• Subjects: 5' Untranslated Regions - genetics; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Case-Control Studies; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Diabetic Retinopathy - genetics; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Eye and associated structures. Visual pathways and centers. Vision; Female; Fundamental and applied biological sciences. Psychology; Haplotypes; Humans; Introns - genetics; Male; Medical sciences; Middle Aged; Ophthalmology; Polymorphism, Single Nucleotide; Retinopathies; Vascular Endothelial Growth Factor A - genetics; Vertebrates: nervous system and sense organs
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.07-1383

To determine whether single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) gene are associated with severity of diabetic retinopathy. A case-control study was conducted in which 45 individuals with type 1 or 2 diabetes with proliferative diabetic retinopathy (PDR) and 61 individuals with type 1 or 2 diabetes without retinopathy (DWR) were genotyped for 14 SNPs in the VEGF promoter and gene. Three of the promoter SNP genotypes, -160C, -152A (rs13207351), and -116A (rs1570360), showed significant independent associations with PDR, as well as the minihaplotype CAA (P = 0.00017). Two promoter haplotypes were associated with severity of retinopathy: -460C, -417T, -172C, -165C, -160C, -152A, -141A, -116A, +405C was associated with PDR (OR [95% CI] = 29.92 [3.91, 228.78], P = 1.62 x 10(-5)) and -460C, -2417T, -172C, -165C, -160C, -152A, -141A, -116G, +405G was associated with DWR (OR = 0.05 [0.01, 0.35], P = 0.000373). Furthermore, two haplotype-tagged (ht) SNPs, +4618 (rs735286) and +5092 (rs2146323), and five htSNP haplotypes were associated with severity of retinopathy. When the nine promoter/5' untranslated region [UTR] and five htSNP genotypes were combined into a 14-SNP haplotype, a single haplotype, -460C, -417T, -172C, -165C, -160C, -152A, -141A, -116A, +405C, +674T, +4618C, +5092A, +9162C, +9512C was found to be significantly associated with the PDR group (OR = 18.45 [2.35, 144.67], P = 0.00622). A clear association was demonstrated between VEGF SNPs and severity of diabetic retinopathy. Furthermore, two of the htSNP haplotypes appear to be more generalized markers for angiogenesis, in that these have been found in prior work to be associated with neovascular age-related macular degeneration.