Decreased mitochondrial D-loop region methylation mediates an increase in mitochondrial DNA copy number in CADASIL.
Decreased mitochondrial D-loop region methylation mediates an increase in mitochondrial DNA copy number in CADASIL.
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CADASIL 中线粒体 D 环区域甲基化减少介导线粒体 DNA 拷贝数增加
DOI：
10.1186/s13148-021-01225-z
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发表时间：
2022-01-04
影响因子：
5.7
通讯作者：
Yan X
中科院分区：
文献类型：
--
作者：
Zhang J;Shang J;Wang F;Huo X;Sun R;Ren Z;Wang W;Yang M;Li G;Gao D;Liu R;Bai P;Wang S;Wang Y;Yan X
伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（CADASIL）是一种典型的与线粒体功能障碍相关的神经退行性疾病。D环区甲基化和线粒体DNA拷贝数（mtDNAcn）在维持线粒体功能中起着关键作用。然而，D-环区甲基化、mtDNA和CADASIL之间的关联仍不清楚。总共招募了162人，包括66名CADASIL患者和96名年龄和性别匹配的对照。从外周白色血细胞中提取基因组DNA后，分别使用MethylTarget测序和实时PCR评估D-环甲基化和mtDNA水平。我们观察到与对照组相比，CADASIL患者的mtDNA Acn增加，D环甲基化水平降低，无论性别分层如何。此外，我们发现D-环甲基化水平与mtDNA呈负相关。介导效应分析显示，mtDNA Acn与CADASIL之间由D环甲基化介导的关联比例为11.6%（95%CI 5.6，22.6）。性别分层后，男性和女性中由D环甲基化介导的这种关联的比例分别为7.2%（95%CI 2.4，19.8）和22.0%（95%CI 7.4，50.1）。CADASIL中D环区甲基化降低介导mtDNA增加，这可能是由CADASIL患者线粒体功能障碍的代偿机制引起的。在线版本包含补充材料，可通过10.1186/s13148-021-01225-z获得。
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a typical neurodegenerative disease associated with mitochondrial dysfunction. Methylation of the D-loop region and mitochondrial DNA copy number (mtDNAcn) play a critical role in the maintenance of mitochondrial function. However, the association between D-loop region methylation, mtDNAcn and CADASIL remains unclear. Overall, 162 individuals were recruited, including 66 CADASIL patients and 96 age- and sex-matched controls. After extracting genomic DNA from the peripheral white blood cells, levels of D-loop methylation and mtDNAcn were assessed using MethylTarget sequencing and real-time PCR, respectively. We observed increased mtDNAcn and decreased D-loop methylation levels in CADASIL patients compared to the control group, regardless of gender stratification. Besides, we found a negative correlation between D-loop methylation levels and mtDNAcn. Mediation effect analysis shows that the proportion of the association between mtDNAcn and CADASIL that is mediated by D-loop methylation is 11.6% (95% CI 5.6, 22.6). After gender stratification, the proportions of such associations that are mediated by D-loop methylation in males and females were 7.2% (95% CI 2.4, 19.8) and 22.0% (95% CI 7.4, 50.1), respectively. Decreased methylation of the D-loop region mediates increased mtDNAcn in CADASIL, which may be caused by a compensatory mechanism of mitochondrial dysfunction in patients with CADASIL. The online version contains supplementary material available at 10.1186/s13148-021-01225-z.
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影响因子：
11.4
作者：
Brown, Jamelle A.;Sammy, Melissa J.;Ballinger, Scott W.
通讯作者：
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线粒体 DNA 置换环区域的甲基化调节结直肠癌中的线粒体拷贝数
影响因子：
3.4
作者：
Tong H;Zhang L;Gao J;Wen S;Zhou H;Feng S
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Feng S
DOI：
10.1146/annurev-genom-082509-141720
发表时间：
2010
影响因子：
8.7
作者：
Calvo SE;Mootha VK
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Mootha VK
影响因子：
3.5
作者：
Sbisà, E;Tanzariello, F;Saccone, C
通讯作者：
Saccone, C
影响因子：
6.6
作者：
Hanemaaijer, Evelyn S.;Panahi, Mahmod;Behbahani, Homira
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