Elevation of peripheral BDNF promoter methylation links to the risk of Alzheimer's disease.

Elevation of peripheral BDNF promoter methylation links to the risk of Alzheimer's disease.
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DOI:
10.1371/journal.pone.0110773
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Wang Q
Wang Q
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chang L;Wang Y;Ji H;Dai D;Xu X;Jiang D;Hong Q;Ye H;Zhang X;Zhou X;Liu Y;Li J;Chen Z;Li Y;Zhou D;Zhuo R;Zhang Y;Yin H;Mao C;Duan S;Wang Q

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脑源性神经营养因子(BDNF)在阿尔茨海默病(AD)等多种精神障碍或疾病中发挥重要作用。我们研究的目的是评估外周血中BDNF启动子甲基化是否能够预测AD的风险。在当前的病例对照研究中,共招募了44名AD患者和62名年龄和性别匹配的对照组。利用亚硫酸氢盐焦磷酸测序技术,我们对BDNF启动子上的4个CpG位点进行了鉴定。结果显示AD患者脑源性神经营养因子甲基化水平显著高于对照组(CpG1:P = 10.021;CpG2:P = 0.002;CpG3:P = 0.007;CpG4:P = 0.005;平均甲基化:P = 0.004)。此外,男性血清碱性磷酸酶、葡萄糖、脂蛋白(A)、载脂蛋白E和载脂蛋白A水平与脑源性神经营养因子启动子甲基化显著相关(碱性磷酸酶:r = −0.308,p = 0.042;葡萄糖:r = −0.383,p = 0.010;脂蛋白(A):r = 0.333,p = 0.027;载脂蛋白E:r = −0.345,p = 0.032;)、女性载脂蛋白A水平(r = 0.362,p = 0.033)和C反应蛋白水平(男性:r = −0.373,p = 0.016;女性:r = −0.399,p = 0.021)。我们的工作表明,外周BDNF启动子甲基化可能是AD风险的诊断标志,尽管其潜在功能仍需在未来详细阐述。
Brain derived neurotrophic factor (BDNF) has been known to play an important role in various mental disorders or diseases such as Alzheimer's disease (AD). The aim of our study was to assess whether BDNF promoter methylation in peripheral blood was able to predict the risk of AD. A total of 44 AD patients and 62 age- and gender-matched controls were recruited in the current case-control study. Using the bisulphite pyrosequencing technology, we evaluated four CpG sites in the promoter of the BDNF. Our results showed that BDNF methylation was significantly higher in AD cases than in the controls (CpG1: p = 10.021; CpG2: p = 0.002; CpG3: p = 0.007; CpG4: p = 0.005; average methylation: p = 0.004). In addition, BDNF promoter methylation was shown to be significantly correlated with the levels of alkaline phosphatase (ALP), glucose, Lp(a), ApoE and ApoA in males (ALP: r = −0.308, p = 0.042; glucose: r = −0.383, p = 0.010; Lp(a): r = 0.333, p = 0.027; ApoE: r = −0.345, p = 0.032;), ApoA levels in females (r = 0.362, p = 0.033), and C Reactive Protein (CRP) levels in both genders (males: r = −0.373, p = 0.016; females: r = −0.399, p = 0.021). Our work suggested that peripheral BDNF promoter methylation might be a diagnostic marker of AD risk, although its underlying function remains to be elaborated in the future.
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