DNA Methylation Analysis in Monozygotic Twins Discordant for ALS in Blood Cells.

Autor: Yazar V; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), German Center for Neurodegenerative Diseases, Ulm, Germany., Ruf WP; Department of Neurology, Ulm University, Ulm, Baden-Württemberg, Germany., Knehr A; Department of Neurology, Ulm University, Ulm, Baden-Württemberg, Germany., Günther K; Department of Neurology, Ulm University, Ulm, Baden-Württemberg, Germany., Ammerpohl O; Institute of Human Genetics, Ulm University & Ulm University Medical Center, Ulm, Germany., Danzer KM; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), German Center for Neurodegenerative Diseases, Ulm, Germany.; Department of Neurology, Ulm University, Ulm, Baden-Württemberg, Germany., Ludolph AC; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), German Center for Neurodegenerative Diseases, Ulm, Germany.; Department of Neurology, Ulm University, Ulm, Baden-Württemberg, Germany.
Jazyk: angličtina
Zdroj: Epigenetics insights [Epigenet Insights] 2023 May 04; Vol. 16, pp. 25168657231172159. Date of Electronic Publication: 2023 May 04 (Print Publication: 2023).
DOI: 10.1177/25168657231172159
Abstrakt: ALS is a fatal motor neuron disease that displays a broad variety of phenotypes ranging from early fatal courses to slowly progressing and rather benign courses. Such divergence can also be seen in genetic ALS cases with varying phenotypes bearing specific mutations, suggesting epigenetic mechanisms like DNA methylation act as disease modifiers. However, the epigenotype dictated by, in addition to other mechanisms, DNA methylation is also strongly influenced by the individual's genotype. Hence, we performed a DNA methylation study using EPIC arrays on 7 monozygotic (MZ) twin pairs discordant for ALS in whole blood, which serves as an ideal model for eliminating the effects of the genetic-epigenetic interplay to a large extent. We found one CpG site showing intra-pair hypermethylation in the affected co-twins, which maps to the Glutamate Ionotropic Receptor Kainate Type Subunit 1 gene ( GRIK1) . Additionally, we found 4 DMPs which were subsequently confirmed using 2 different statistical approaches. Differentially methylated regions or blocks could not be detected within the scope of this work. In conclusion, we revealed that despite a low sample size, monozygotic twin studies discordant for the disease can bring new insights into epigenetic processes in ALS, pointing to new target loci for further investigations.
Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
(© The Author(s) 2023.)
Databáze: MEDLINE
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