研究报告:精神分裂症断裂基因1启动子的高甲基化增加阿尔茨海默病的发病风险
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1.1)宁波大学医学院,浙江省病理生理学重点实验室,宁波 315211;2.2)宁波大学医学院附属医院神经内科,宁波 315020;3.3)宁波医疗中心李惠利医院神经内科,宁波 315000;4.4)浙江医药高等专科学校,宁波 315000;5.5)宁波大学医学院附属医院麻醉科,宁波 315020

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基金项目:

国家自然科学基金(81771166,U1503223),浙江省自然科学基 金(LY20H090004),宁波市科技局计划项目(202002N3165),浙 江省医药卫生科技计划(2020KY855),宁波市自然科学基金 (2019A610290, 2019A610295) , 宁波市公益科技项目 (202002N3141),浙江省中医药科技项目(2020ZB236) 和宁波大 学王宽诚幸福基金资助项目。


Research: Elevated DISC1 Promoter Methylation Increases The Risk of Alzheimer’s Disease
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1.1)Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China;2.2)Department of Neurology, the Affiliated Hospital of Medical School, Ningbo University, Ningbo 315020, China;3.3)Department of Neurology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, China;4.4)Zhejiang Pharmaceutical College, Ningbo 315000, China;5.5)Department of Anesthesiology, the Affiliated Hospital of Medical School, Ningbo University, Ningbo 315020, China

Fund Project:

This work was supported by grants from The National Natural Science Foundation of China (81771166, U1503223), Natural Science Foundation of Zhejiang Province (LY20H090004), Ningbo Science and Technology Plan Project (202002N3165), the Medicine and Health Science and Technology Plan Project of Zhejiang Province (2020KY855), Natural Science Foundation of Ningbo City (2019A61029, 2019A610295), Ningbo Public Welfare Science and Technology Plan Project (202002N3141), Zhejiang Science and Technology Plan of Traditional Chinese Medicine (2020ZB236) and the K.C.Wong Magna Fund in Ningbo University.

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    摘要:

    目的 基因的表观修饰与阿尔茨海默病(AD)的发生密切相关,精神分裂症断裂基因1(disrupted in schizophrenia 1,DISC1)是AD的候选基因。然而DISC1启动子甲基化与AD发生的关系尚不清楚。方法 采用亚硫酸氢盐转化后焦磷酸测序分析的方法检测中国汉族51例AD患者和63例健康对照者血液样本中DISC1的甲基化水平。采用标准方法检测血样中各生化指标。结果 AD组DISC1的甲基化水平显著高于健康对照组(P=0.002)。载脂蛋白A(apolipoprotein A,ApoA)、血清脂蛋白(lipoprotein A,Lp(a))和DISC1 CpG3甲基化之间发现了显著的关联。其中,女性AD患者中DISC1甲基化与血浆ApoA水平呈正相关(P=0.010,P=0.003)。男性AD患者中DISC1甲基化与血浆Lp(a)水平呈正相关(P<0.000 1)。DISC1启动子甲基化的曲线下面积(area under curve,AUC)为0.726(95% CI:0.626~0.827),灵敏度和特异度分别为0.569和0.869。结论 外周血DISC1启动子高甲基化是AD发生的高风险因素,其可能是AD诊断的潜在生物标志物。

    Abstract:

    Objective Aberrant promoter methylation of multiple genes is associated with various diseases, including Alzheimer’s disease (AD), however, the relationship between disrupted-in-schizophrenia-1 (DISC1) promoter methylation and the progress of AD is unclear.Methods The methylation levels of the DISC1 promoter were measured in 51 AD patients and 63 controls using bisulfite pyrosequencing assay. Blood biochemical indicators were detected using standard methods.Results DISC1 promoter methylation was significantly higher in AD patients than in controls (P=0.002). Moreover, Both apolipoprotein A (ApoA) and Lipoprotein A (Lp(a)) are significantly correlated with the DISC1 CpG3 methylation. DISC1 methylation is positively correlated with blood ApoA in female (P=0.003). DISC1 methylation is positively correlated with blood Lp(a) in male (P<0.000 1). The area under curve (AUC) of DISC1 promoter methylation is 0.726 (95% CI: 0.626-0.827), the sensitivity is 0.560 and specificity is 0.869.Conclusion The results of the present study demonstrated that elevated DISC1 promoter methylation was associated with AD risk in males, and it may be a potential biomarker for the diagnosis of AD.

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鲍荣荣,陈韦华,王欣,许春双,牛艳芳,王芳,楼琼,宋飞,朱斌斌,王钦文,徐淑君.研究报告:精神分裂症断裂基因1启动子的高甲基化增加阿尔茨海默病的发病风险[J].生物化学与生物物理进展,2022,49(4):668-674

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历史
  • 收稿日期:2021-06-29
  • 最后修改日期:2021-08-20
  • 接受日期:2021-10-08
  • 在线发布日期: 2022-04-22
  • 出版日期: 2022-04-20