Journal
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
Volume 19, Issue 1-2, Pages 93-101Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/21678421.2017.1367401
Keywords
Amyotrophic lateral sclerosis; superoxide dismutase 1; DNA methylation; epigenetics
Categories
Funding
- ASSOCIAZIONE IO CORRO CON GIOVANNI
- Paina di Giussano - Via IV Novembre 20 c/o Centro Associativo Generazioni
Ask authors/readers for more resources
Objective: More than 180 different superoxide dismutase 1 (SOD1) mutations have been described to date in amyotrophic lateral sclerosis (ALS) patients, including not completely penetrant ones leading to phenotypic heterogeneity among carriers. We collected DNA samples from five ALS families with not fully penetrant SOD1 mutations (p.Asn65Ser, p.Gly72Ser, p.Gly93Asp, and p.Gly130_Glu133del) searching for epigenetic differences among ALS patients, asymptomatic/paucisymptomatic carriers and non-carrier family members. Methods: Global DNA methylation levels (5-methylcytosine levels) were determined in blood DNA samples with an enzyme-linked immunosorbent assay (ELISA), and the methylation analysis of SOD1, FUS, TARDBP and C9orf72 genes was performed using Methylation-Sensitive High-Resolution Melting (MS-HRM) technique. Results: Global DNA methylation levels were significantly higher in blood DNA of ALS patients than in asymptomatic/paucisymptomatic carriers or family members non-carriers of SOD1 mutations, and a positive correlation between global DNA methylation levels and disease duration (months) was observed. SOD1, FUS, TARDBP and C9orf72 gene promoters were demethylated in all subjects. Conclusions: The present study suggests that global changes in DNA methylation might contribute to the ALS phenotype in carriers of not fully penetrant SOD1 mutations, thus reinforcing the role of epigenetic factors in modulating the phenotypic expression of the disease.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available