Mitochondrial DNA copy number and D-loop region methylation in carriers of amyotrophic lateral sclerosis gene mutations

• Published in: Epigenomics Vol. 10; no. 11; pp. 1431 - 1443
• Main Authors: Stoccoro, Andrea, Mosca, Lorena, Carnicelli, Vittoria, Cavallari, Ugo, Lunetta, Christian, Marocchi, Alessandro, Migliore, Lucia, Coppedè, Fabio
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.11.2018
• Subjects: Adult; Aged; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - genetics; C9orf72 Protein - genetics; Copy number; D-loop mitochondrial region; Demethylation; Deoxyribonucleic acid; DNA; DNA Copy Number Variations; DNA Methylation; DNA, Mitochondrial - genetics; DNA-Binding Proteins - genetics; epigenetics; Female; Heterozygote; Humans; Male; Middle Aged; Mitochondrial DNA; mitochondrial DNA methylation; mtDNA copy number; Mutation; Neurodegeneration; RNA-Binding Protein FUS - genetics; Superoxide dismutase; Superoxide Dismutase-1 - genetics; Italy; mitochondrial DNA methylation; amyotrophic lateral sclerosis; mtDNA copy number; D-loop mitochondrial region; epigenetics; SOD1
• ISSN: 1750-1911; 1750-192X
• DOI: 10.2217/epi-2018-0072

To investigate mitochondrial DNA (mtDNA) copy number and D-loop region methylation in carriers of , , and mutations. Investigations were performed in blood DNA from 114 individuals, including amyotrophic lateral sclerosis (ALS) patients, presymptomatic carriers and noncarrier family members. Increased mtDNA copy number (p = 0.0001) was observed in ALS patients, and particularly in those with or mutations. 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. Demethylation of the D-loop region could represent a compensatory mechanism for mtDNA upregulation in carriers of ALS-linked mutations.