VEGF gene and phenotype relation with Alzheimer's disease and mild cognitive impairment
VEGF gene and phenotype relation with Alzheimer's disease and mild cognitive impairment
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DOI：
10.1089/rej.2006.9.485
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发表时间：
2006-12-01
影响因子：
2.6
通讯作者：
Licastro, Federico
中科院分区：
文献类型：
--
作者：
Chiappelli, Martina;Borroni, Barbara;Licastro, Federico
背景资料：血管内皮生长因子（VEGF）的表达代表了血管和阿尔茨海默病（AD）病理学相关的一种潜在机制。作者调查了AD病例，特别是那些具有快速认知能力下降的病例，是否更常见地携带VEGF的功能性启动子基因变体（-2578C/A），并显示血浆VEGF水平升高。此外，作者还调查了轻度认知障碍（MCI）和从MCI向AD的转化是否也存在相关模式。方法：第一组包括317例AD患者和320例健康对照者。第2组包括113名MCI患者和130名对照受试者。通过化学发光测量第1组亚组的血浆VEGF水平。对所有受试者进行基因型测定。结果：VEGF AA基因型与AD发生风险增加相关（OR = 1.616，p = 0.046）。该基因型还与APOE β 4阳性AD患者的认知能力下降加速相关（AA vs. CC OR = 6.5，p = 0.04）。VEGF AA基因型是MCI（OR = 2.5，p = 0.037）和APOE β 4+患者MCI转化为AD（OR = 6.5，CI = 2.014-20.980; p = 0.002）的风险因素。AD患者的VEGF血浆水平高于对照组（230 pg/mL vs. 42 pg/mL），并且在具有快速认知下降和APOE β 4等位基因的患者中甚至更高。解释：VEGF表达的调节是与AD发生及其临床恶化风险相关的潜在机制。
Background: The expression of vascular endothelial growth factor (VEGF) represents one potential mechanism whereby vascular and Alzheimer's disease (AD) pathologies are related. The authors investigated whether AD cases, especially those having a rapid cognitive decline, more commonly carried a functional promoter gene variant for VEGF (-2578C/A) and showed elevated plasma levels of Vegf. In addition, the authors investigated whether patterns of association also were found for mild cognitive impairment (MCI) and conversion from MCI to AD. Methods: Group 1 included 317 AD cases and 320 unaffected control subjects. Group 2 included 113 MCI patients and 130 control subjects. Plasma levels of Vegf were measured by chemiluminescence for a subset of group 1. Genotype determinations were made for all subjects. Findings: The VEGF AA genotype was associated with an increased risk of developing AD (OR = 1.616, p = 0.046). This genotype also was associated with an accelerated cognitive decline in APOE epsilon 4 positive patients with AD (AA vs. CC OR = 6.5, p = 0.04). The VEGF AA genotype was a risk factor for MCI (OR = 2.5, p = 0.037) and MCI conversion to AD in APOE epsilon 4+ (OR = 6.5, Cl = 2.014-20.980; p = 0.002). Vegf plasma levels were higher in patients with AD than controls (230 pg/mL vs. 42 pg/mL), and were even higher in those patients with a fast cognitive decline and the APOE epsilon 4 allele. Interpretation: Modulation of VEGF expression is a potential mechanism associated with the risk of developing AD and its clinical deterioration.