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- Title
Genome-wide DNA methylation analysis related to ALS patient progression and survival.
- Authors
Yang, Tianmi; Li, Chunyu; Wei, Qianqian; Pang, Dejiang; Cheng, Yangfan; Huang, Jingxuan; Lin, Junyu; Xiao, Yi; Jiang, Qirui; Wang, Shichan; Shang, Huifang
- Abstract
Background: Epigenetics contributes to the pathogenesis of amyotrophic lateral sclerosis (ALS). We aimed to characterize the DNA methylation profiles associated with clinical heterogeneity in disease progression and survival among patients. Methods: We included a cohort of 41 patients with sporadic ALS, with a median follow-up of 86.9 months, and 27 rigorously matched healthy controls. Blood-based genome-wide DNA methylation analysis was conducted. Results: A total of 948 progression rate-associated differentially methylated positions, 298 progression rate-associated differentially methylated regions (R-DMRs), 590 survival time-associated DMPs, and 197 survival time-associated DMRs (S-DMRs) were identified, using complementary grouping strategies. Enrichment analysis of differentially methylated genes highlighted the involvement of synapses and axons in ALS progression and survival. Clinical analysis revealed a positive correlation between the average methylation levels of the R-DMR in PRDM8 and disease progression rate (r = 0.479, p = 0.002). Conversely, there was an inverse correlation between the average methylation levels of the R-DMR in ANKRD33 and disease progression rate (r = − 0.476, p = 0.002). In addition, patients with higher methylation levels within the S-DMR of ZNF696 experienced longer survival (p = 0.016), while those with elevated methylation levels in the S-DMR of RAI1 had shorter survival (p = 0.006). Conclusion: DNA methylation holds promise as a potential biomarker for tracking disease progression and predicting survival outcome and also offers targets for precision medicine.
- Subjects
DNA methylation; DNA analysis; AMYOTROPHIC lateral sclerosis; DISEASE progression; GENE ontology; SURVIVAL rate; DEMETHYLATION
- Publication
Journal of Neurology, 2024, Vol 271, Issue 5, p2672
- ISSN
0340-5354
- Publication type
Article
- DOI
10.1007/s00415-024-12222-6