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- Title
Decreased mitochondrial D-loop region methylation mediates an increase in mitochondrial DNA copy number in CADASIL.
- Authors
Zhang, Jiewen; Shang, Junkui; Wang, Fengyu; Huo, Xuejing; Sun, Ruihua; Ren, Zhixia; Wang, Wan; Yang, Miaomiao; Li, Gai; Gao, Dandan; Liu, Ruijie; Bai, Pingping; Wang, Shuyi; Wang, Yanliang; Yan, Xi
- Abstract
Background: 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. Methods: 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. Results: 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. Conclusion: 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.
- Subjects
MITOCHONDRIAL DNA; METHYLATION; LEUCOCYTES; MITOCHONDRIA; GENDER inequality
- Publication
Clinical Epigenetics, 2022, Vol 14, Issue 1, p1
- ISSN
1868-7075
- Publication type
Article
- DOI
10.1186/s13148-021-01225-z