Churchill Amanda J, Carter James G, Ramsden Conor, Turner Steven J, Yeung Anna, Brenchley Paul E C, Ray David W
Unit of Ophthalmology, Bristol Eye Hospital, University of Bristol, Bristol, United Kingdom.
Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3611-6. doi: 10.1167/iovs.07-1383. Epub 2008 Apr 25.
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.
确定血管内皮生长因子（VEGF）基因中的单核苷酸多态性（SNP）是否与糖尿病视网膜病变的严重程度相关。
进行了一项病例对照研究，对45例患有1型或2型糖尿病且伴有增殖性糖尿病视网膜病变（PDR）的患者以及61例患有1型或2型糖尿病但无视网膜病变（DWR）的患者进行了VEGF启动子和基因中14个SNP的基因分型。
三种启动子SNP基因型，即-160C、-152A（rs13207351）和-116A（rs1570360），以及微型单倍型CAA（P = 0.00017）与PDR显示出显著的独立关联。两种启动子单倍型与视网膜病变的严重程度相关：-460C、-417T、-172C、-165C、-160C、-152A、-141A、-116A、+405C与PDR相关（比值比[95%可信区间]=29.92[3.91, 228.78]，P = 1.62×10⁻⁵），而-460C、-2417T、-172C、-165C、-160C、-152A、-141A、-116G、+（此处原文有误，推测应为+405G）与DWR相关（比值比=0.05[0.01, 0.35]，P = 0.000373）。此外，两个单倍型标签（ht）SNP，即+4618（rs735286）和+5092（rs2146323），以及五个htSNP单倍型与视网膜病变的严重程度相关。当将九个启动子/5'非翻译区（UTR）和五个htSNP基因型组合成一个14-SNP单倍型时，发现一个单倍型，即-460C、-417T、-172C、-165C、-160C、-152A、-141A、-116A、+405C、+674T、+4618C、+5092A、+9162C、+9512C与PDR组显著相关（比值比=18.45[2.35, 144.67]，P = 0.00622）。
VEGF SNP与糖尿病视网膜病变的严重程度之间存在明确关联。此外，两个htSNP单倍型似乎是更普遍的血管生成标志物，因为在先前的研究中发现它们与新生血管性年龄相关性黄斑变性相关。
