DNA methylation in repetitive elements and Alzheimer disease.
DNA methylation in repetitive elements and Alzheimer disease.
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DOI：
10.1016/j.bbi.2011.01.017
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发表时间：
2011-08
影响因子：
15.1
通讯作者：
Baccarelli, A.
中科院分区：
文献类型：
--
作者：
Bollati, V.;Galimberti, D.;Pergoli, L.;Dalla Valle, E.;Barretta, F.;Cortini, F.;Scarpini, E.;Bertazzi, P. A.;Baccarelli, A.
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，是一种可逆机制，通过将甲基添加到位于CpG二核苷酸中的胞嘧啶以形成5甲基胞嘧啶（5 mC）来改变基因组功能和染色体稳定性。重复元件（即Alu，LINE-1和SAT- α）的甲基化状态是全球DNA甲基化模式的主要贡献者，并已被研究与多种人类疾病有关。然而，迄今为止，AD患者血液中重复元件甲基化的作用从未被研究过。本研究采用亚硫酸氢盐-PCR焦磷酸测序法检测了43例AD患者和38例健康志愿者的Alu、LINE-1和SAT- α基因甲基化水平。在调整年龄和性别的多变量分析中，与健康志愿者相比，AD患者的LINE-1增加（AD：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显示出更高水平的LINE-1甲基化（MMSE>22：83.9%5mC; MMSE<=22：83.2%5mC; p=0.05）。我们的数据表明，LINE-1甲基化可能会导致更好地了解AD的发病机制和过程，并可能有助于确定新的标记物，用于评估风险分层。进一步的前瞻性研究是必要的，以评估从早期AD到疾病晚期的DNA甲基化动态。
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.
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DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
影响因子：
4.2
作者：
Fuso, Andrea;Nicolia, Vincenzina;Scarpa, Sigfrido
通讯作者：
Scarpa, Sigfrido
影响因子：
11.4
作者：
Petronis, A
通讯作者：
Petronis, A
影响因子：
11.2
作者：
Bollati, Valentina;Baccarelli, Andrea;Yang, Allen S.
通讯作者：
Yang, Allen S.
DOI：
10.1073/pnas.0500398102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Fraga, MF;Ballestar, E;Esteller, M
通讯作者：
Esteller, M