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Article

Differential Methylation in the GSTT1 Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy

1
Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, Denmark
2
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, Denmark
3
Section of Forensic Pathology, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, Denmark
4
The Heart Centre, Department of Cardiology, Copenhagen University Hospital Rigshospitalet, DK-1353 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: Ralph Knöll
Int. J. Mol. Sci. 2021, 22(6), 2790; https://doi.org/10.3390/ijms22062790
Received: 30 January 2021 / Revised: 27 February 2021 / Accepted: 4 March 2021 / Published: 10 March 2021
(This article belongs to the Special Issue Epigenetic Mechanisms of Cardiac Disease)
Sudden cardiac death (SCD) is a diagnostic challenge in forensic medicine. In a relatively large proportion of the SCDs, the deaths remain unexplained after autopsy. This challenge is likely caused by unknown disease mechanisms. Changes in DNA methylation have been associated with several heart diseases, but the role of DNA methylation in SCD is unknown. In this study, we investigated DNA methylation in two SCD subtypes, sudden unexplained death (SUD) and sudden unexpected death in epilepsy (SUDEP). We assessed DNA methylation of more than 850,000 positions in cardiac tissue from nine SUD and 14 SUDEP cases using the Illumina Infinium MethylationEPIC BeadChip. In total, six differently methylated regions (DMRs) between the SUD and SUDEP cases were identified. The DMRs were located in proximity to or overlapping genes encoding proteins that are a part of the glutathione S-transferase (GST) superfamily. Whole genome sequencing (WGS) showed that the DNA methylation alterations were not caused by genetic changes, while whole transcriptome sequencing (WTS) showed that DNA methylation was associated with expression levels of the GSTT1 gene. In conclusion, our results indicate that cardiac DNA methylation is similar in SUD and SUDEP, but with regional differential methylation in proximity to GST genes. View Full-Text
Keywords: epigenetics; genetics; DNA methylation; RNA; molecular autopsy; sudden cardiac death; sudden unexplained death; sudden unexpected death in epilepsy epigenetics; genetics; DNA methylation; RNA; molecular autopsy; sudden cardiac death; sudden unexplained death; sudden unexpected death in epilepsy
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MDPI and ACS Style

Christiansen, S.N.; Jacobsen, S.B.; Andersen, J.D.; Kampmann, M.-L.; Trudsø, L.C.; Olsen, K.B.; Tfelt-Hansen, J.; Banner, J.; Morling, N. Differential Methylation in the GSTT1 Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy. Int. J. Mol. Sci. 2021, 22, 2790. https://doi.org/10.3390/ijms22062790

AMA Style

Christiansen SN, Jacobsen SB, Andersen JD, Kampmann M-L, Trudsø LC, Olsen KB, Tfelt-Hansen J, Banner J, Morling N. Differential Methylation in the GSTT1 Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy. International Journal of Molecular Sciences. 2021; 22(6):2790. https://doi.org/10.3390/ijms22062790

Chicago/Turabian Style

Christiansen, Steffan N., Stine B. Jacobsen, Jeppe D. Andersen, Marie-Louise Kampmann, Linea C. Trudsø, Kristine B. Olsen, Jacob Tfelt-Hansen, Jytte Banner, and Niels Morling. 2021. "Differential Methylation in the GSTT1 Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy" International Journal of Molecular Sciences 22, no. 6: 2790. https://doi.org/10.3390/ijms22062790

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