Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
Brain Behav Immun. 2011 Aug;25(6):1078-83. doi: 10.1016/j.bbi.2011.01.017. Epub 2011 Feb 3.
Epigenetics is believed to play a role in Alzheimer's disease (AD). DNA methylation, the most investigated epigenetic hallmark, is a reversible mechanism that modifies genome function and chromosomal stability through the addition of methyl groups to cytosine located in CpG dinucleotides to form 5 methylcytosine (5mC). Methylation status of repetitive elements (i.e. Alu, LINE-1 and SAT-α) is a major contributor of global DNA methylation patterns and has been investigated in relation to a variety of human diseases. However, the role of methylation of repetitive elements in blood of AD patients has never been investigated so far. In the present study, a quantitative bisulfite-PCR pyrosequencing method was used to evaluate methylation of Alu, LINE-1 and SAT-α sequences in 43 AD patients and 38 healthy donors. In multivariate analysis adjusting for age and gender, LINE-1 was increased in AD patients compared with healthy volunteers (ADs: 83.6%5mC, volunteers: 83.1%5mC, p-value: 0.05). The group with best performances in mini mental state examination (MMSE) showed higher levels of LINE-1 methylation compared to the group with worst performances (MMSE>22: 83.9%5mC; MMSE≤22: 83.2%5mC; p=0.05). Our data suggest that LINE-1 methylation may lead to a better understanding of AD pathogenesis and course, and may contribute to identify novel markers useful to assess risk stratification. Further prospective investigations are warranted to evaluate the dynamics of DNA methylation from early-stage AD to advanced phases of the disease.
表观遗传学被认为在阿尔茨海默病（AD）中起作用。DNA 甲基化是研究最多的表观遗传标志，是一种通过向位于 CpG 二核苷酸中的胞嘧啶添加甲基基团来修饰基因组功能和染色体稳定性的可逆机制，形成 5-甲基胞嘧啶（5mC）。重复元件（即 Alu、LINE-1 和 SAT-α）的甲基化状态是全基因组甲基化模式的主要贡献者，并已在多种人类疾病中进行了研究。然而，迄今为止，尚未研究 AD 患者血液中重复元件甲基化的作用。在本研究中，使用定量亚硫酸氢盐-PCR 焦磷酸测序法评估了 43 名 AD 患者和 38 名健康供体中 Alu、LINE-1 和 SAT-α 序列的甲基化。在调整年龄和性别因素的多变量分析中，与健康志愿者相比，AD 患者的 LINE-1 增加（ADs：83.6%5mC，志愿者：83.1%5mC，p 值：0.05）。在简易精神状态检查（MMSE）中表现最好的组与表现最差的组相比，LINE-1 甲基化水平更高（MMSE>22：83.9%5mC；MMSE≤22：83.2%5mC；p=0.05）。我们的数据表明，LINE-1 甲基化可能有助于更好地理解 AD 的发病机制和病程，并有助于识别有助于评估风险分层的新标志物。需要进一步的前瞻性研究来评估从早期 AD 到疾病晚期的 DNA 甲基化动态。
