Chen Wei, Zhou Xiaohui, Duan Yali, Zou Ting, Liu Guili, Ying Xiuru, Wang Qinwen, Duan Shiwei
Department of Internal Medicine for Cadres, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, Xinjiang 830000, P.R. China.
Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
Exp Ther Med. 2018 Oct;16(4):3135-3142. doi: 10.3892/etm.2018.6524. Epub 2018 Jul 26.
Alzheimer's disease (AD) is a neurodegenerative disorder leading to progressive memory and cognitive impairment. Previous studies have identified multiple genes associated with AD. The aim of the present study was to validate the association of the five AD-associated variants, 8-oxoguanine DNA glycosylase 1 () rs1052133, bridging integrator 1 rs744373, sortilin-related receptor 1, rs1133174, presenilin 2 rs8383, and nerve growth factor rs6330, in the Xinjiang Chinese population. In addition, the present study evaluated the contribution of the promoter methylation of two genes, and dihydrolipoamide succinyltransferase () to the risk of AD. A total of 17 AD cases and 34 controls were recruited from Xinjiang province in China. Genotyping was done by Sanger sequencing. DNA methylation assay was performed using quantitative methylation specific polymerase chain reaction. The study was unable to repeat the previous association of the five genetic polymorphisms with AD. However, methylation levels were demonstrated to be significantly decreased in AD patients (P=0.027), particularly in female AD patients (P=0.025). Subgroup analysis by apolipoprotein E ( ε4) genotype demonstrated that methylation levels were significantly increased in non-ε4 carriers compared with ε4 carriers (P=0.027). In summary, the present study reported that hypomethylation was significantly associated with AD in females, and that promoter methylation may interact with ε4 genotype.
阿尔茨海默病（AD）是一种导致进行性记忆和认知障碍的神经退行性疾病。先前的研究已经鉴定出多个与AD相关的基因。本研究的目的是在新疆汉族人群中验证五个与AD相关的变异体，即8-氧代鸟嘌呤DNA糖基化酶1（）rs1052133、桥连整合器1 rs744373、sortilin相关受体1 rs1133174、早老素2 rs8383和神经生长因子rs6330之间的关联。此外，本研究评估了两个基因，即和二氢硫辛酰胺琥珀酰转移酶（）的启动子甲基化对AD风险的影响。在中国新疆地区共招募了17例AD患者和34名对照。通过桑格测序进行基因分型。使用定量甲基化特异性聚合酶链反应进行DNA甲基化检测。该研究未能重复先前报道的五个基因多态性与AD的关联。然而，研究表明，AD患者的甲基化水平显著降低（P = 0.027），尤其是女性AD患者（P = 0.025）。载脂蛋白E（ε4）基因型亚组分析表明，与ε4携带者相比，非ε4携带者的甲基化水平显著升高（P = 0.027）。总之，本研究报告称，女性中甲基化不足与AD显著相关，并且启动子甲基化可能与ε4基因型相互作用。
