Genome-Wide DNA Methylation Profiling Reveals Low Methylation Variability in Moyamoya Disease.

Autor: Tokairin K; Department of Neurosurgery, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA, 94305, USA.; Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA, USA., Ito M; Department of Neurosurgery, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA, 94305, USA.; Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA, USA., Lee AG; Division of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, CA, USA., Teo M; Department of Neurosurgery, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA, 94305, USA.; Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA, USA., He S; Department of Neurosurgery, Peking Union Medical College Hospital, Peking, China., Cheng MY; Department of Neurosurgery, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA, 94305, USA. mycheng@stanford.edu.; Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA, USA. mycheng@stanford.edu., Steinberg GK; Department of Neurosurgery, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA, 94305, USA. gsteinberg@stanford.edu.; Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA, USA. gsteinberg@stanford.edu.
Jazyk: angličtina
Zdroj: Translational stroke research [Transl Stroke Res] 2024 Oct 02. Date of Electronic Publication: 2024 Oct 02.
DOI: 10.1007/s12975-024-01299-w
Abstrakt: Moyamoya disease (MMD) is a chronic cerebrovascular disorder that can lead to stroke and neurological dysfunctions. Given the largely sporadic nature and the role of gene-environment interactions in various diseases, we examined epigenetic modifications in MMD. We performed genome-wide DNA methylation using Illumina 850 K Methylation EPIC BeadChip, in two racially distinct adult female cohorts: a non-Asian cohort (13 MMD patients and 7 healthy controls) and an Asian cohort (14 MMD patients and 3 healthy controls). An additional external cohort with both sexes (females: 5 MMD patients and 5 healthy controls, males: 5 MMD patients and 5 healthy controls) was included for validation. Our findings revealed strikingly low DNA methylation variability between MMD patients and healthy controls, in both MMD female cohorts. In the non-Asian cohort, only 6 probes showed increased variability versus 647 probes that showed decreased variability. Similarly, in the Asian cohort, the MMD group also displayed a reduced methylation variability across all 2845 probes. Subsequent analysis showed that these differentially variable probes are located on genes involved in key biological processes such as methylation and transcription, DNA repair, cytoskeletal remodeling, natural killer cell signaling, cellular growth, and migration. These findings mark the first observation of low methylation variability in any disease, contrasting with the high variability observed in other disorders. This reduced methylation variability in MMD may hinder patients' adaptability to environmental shifts, such as hemodynamic stress, thereby influencing vascular homeostasis and contributing to MMD pathology. These findings offer new insights into the mechanisms of MMD and potential treatment strategies.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: