Mitochondrial DNA copy number and D-loop region methylation in carriers of amyotrophic lateral sclerosis gene mutations. (8th August 2018)

• Record Type: Journal Article
• Authors: Stoccoro, Andrea; Mosca, Lorena; Carnicelli, Vittoria; Cavallari, Ugo; Lunetta, Christian; Marocchi, Alessandro; Migliore, Lucia; Coppedè, Fabio
• Is Part Of: Epigenomics. Volume 10:Number 11(2018)
• Page Start: 1431
• Page End: 1443
• Publication Date: 2018-08-08
• Subjects: amyotrophic lateral sclerosis -- D-loop mitochondrial region -- epigenetics -- mitochondrial DNA methylation -- mtDNA copy number -- SOD1; Epigenesis -- Periodicals; Genomics -- Periodicals; Chromatin -- Periodicals; DNA -- Periodicals; 572.87
• DOI: 10.2217/epi-2018-0072
• Languages: English
• ISSNs: 1750-1911

Abstract

Aim: To investigate mitochondrial DNA (mtDNA) copy number and D-loop region methylation in carriers of SOD1, TARDBP, FUS and C9orf72 mutations.Methods: Investigations were performed in blood DNA from 114 individuals, including amyotrophic lateral sclerosis (ALS) patients, presymptomatic carriers and noncarrier family members.Results: Increased mtDNA copy number (p = 0.0001) was observed in ALS patients, and particularly in those with SOD1 or C9orf72 mutations. SOD1 mutation carriers showed also a significant decrease in D-loop methylation levels (p = 0.003). An inverse correlation between D-loop methylation levels and the mtDNA copy number (p = 0.0005) was observed.Conclusion: Demethylation of the D-loop region could represent a compensatory mechanism for mtDNA upregulation in carriers of ALS-linked SOD1 mutations.