VEGF polymorphisms are associated with neovascular age-related macular degeneration
VEGF polymorphisms are associated with neovascular age-related macular degeneration
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DOI：
10.1093/hmg/ddl238
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发表时间：
2006-10-01
影响因子：
3.5
通讯作者：
Atan, Denize
中科院分区：
文献类型：
--
作者：
Churchill, Amanda J.;Carter, James G.;Atan, Denize
老年性黄斑变性(AMD)是老年人最常见的致盲原因。已经证明与血管内皮生长因子(VEGF)基因有关联，在患有新生血管疾病的个体中，眼睛中的VEGF水平会升高。为了进一步研究血管内皮生长因子的作用，我们进行了一项病例对照研究，其中45例新生血管性AMD患者和94名年龄匹配的对照组进行了血管内皮生长因子启动子和基因的14个单核苷酸多态(SNPs)的基因分型。单基因SNP+674CC型与AMD显著相关(OR=2.40，95%CI1.09~5.26，P=0.027)。SNPs+674、+4618、+5092、+9162和+9512的单倍型分析显示，CTCCT和TCACC与AMD相关(OR=15.77，95%CI1.91~130.24，P=0.0161和OR=9.95，95%CI3.22~30.74，P=0.000053)。单倍型TCACT与对照组相关(P=0.0001832)。启动子SNPs单倍型分析显示-460T、-417T、-172C、-165C、-160C、-152G、-141a、-116A、+405C单倍型与AMD密切相关(OR=18.24，95%CI2.25~148.25，P=0.0074)。这是对AMD中血管内皮生长因子基因的最广泛的分析，表明与渗出型疾病有明显的关联，从而为预测性测试创造了可能性。吸烟、高脂肪摄入和高血压是AMD的负面环境危险因素，而增加饮食抗氧化剂的摄入量可以起到保护作用。识别人群中的高危人群将允许个人咨询和生活方式建议，以减少失明的风险。
Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly. Linkage has been shown to the vascular endothelial growth factor (VEGF) gene and ocular levels of VEGF are raised in individuals with the neovascular form of disease. To examine the role of VEGF further, we conducted a case-control study where 45 individuals with neovascular AMD and 94 age-matched controls were genotyped for 14 single nucleotide polymorphisms (SNPs) in the VEGF promoter and gene. The single SNP +674 CC genotype was significantly associated with AMD (OR=2.40, 95%CI 1.09-5.26, P=0.027). Haplotype analysis of SNPs +674, +4618, +5092, +9162 and +9512 revealed that CTCCT and TCACC were associated with AMD (OR=15.77, 95% CI 1.91-130.24, P=0.0161 and OR=9.95, 95%CI 3.22-30.74, P=0.000053, respectively). The haplotype TCACT was associated with the control group (P=0.0001832). Furthermore, haplotype analysis of promoter SNPs revealed that possession of the -460T, -417T, -172C, -165C, -160C, -152G, -141A, -116A, +405C haplotype was strongly associated with AMD (OR=18.24, 95%CI 2.25-148.25, P=0.0074). This is the most extensive analysis of the VEGF gene in AMD, demonstrating a clear association with the exudative form of disease, thereby creating the possibility for predictive testing. Smoking, high fat intake and hypertension are negative environmental risk factors in AMD, whereas increased consumption of dietary antioxidants can have a protective effect. Identification of those at risk in the population would allow individual counselling with lifestyle advice to reduce the risks of blindness.