Differential Methylation in the <i>GSTT1</i> Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy
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 dise...
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doaj-a9d198574f0b4fa2b66c289775394c262021-03-11T00:00:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01222790279010.3390/ijms22062790Differential Methylation in the <i>GSTT1</i> Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in EpilepsySteffan Noe Christiansen0Stine Bøttcher Jacobsen1Jeppe Dyrberg Andersen2Marie-Louise Kampmann3Linea Christine Trudsø4Kristine Boisen Olsen5Jacob Tfelt-Hansen6Jytte Banner7Niels Morling8Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, DenmarkSection of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, DenmarkSection of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, DenmarkSection of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, DenmarkSection of Forensic Pathology, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, DenmarkSection of Forensic Pathology, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, DenmarkSection of Forensic Pathology, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, DenmarkSection of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1353 Copenhagen, DenmarkSudden 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 <i>GSTT1</i> 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.https://www.mdpi.com/1422-0067/22/6/2790epigeneticsgeneticsDNA methylationRNAmolecular autopsysudden cardiac death |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Steffan Noe Christiansen Stine Bøttcher Jacobsen Jeppe Dyrberg Andersen Marie-Louise Kampmann Linea Christine Trudsø Kristine Boisen Olsen Jacob Tfelt-Hansen Jytte Banner Niels Morling |
spellingShingle |
Steffan Noe Christiansen Stine Bøttcher Jacobsen Jeppe Dyrberg Andersen Marie-Louise Kampmann Linea Christine Trudsø Kristine Boisen Olsen Jacob Tfelt-Hansen Jytte Banner Niels Morling Differential Methylation in the <i>GSTT1</i> Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy International Journal of Molecular Sciences epigenetics genetics DNA methylation RNA molecular autopsy sudden cardiac death |
author_facet |
Steffan Noe Christiansen Stine Bøttcher Jacobsen Jeppe Dyrberg Andersen Marie-Louise Kampmann Linea Christine Trudsø Kristine Boisen Olsen Jacob Tfelt-Hansen Jytte Banner Niels Morling |
author_sort |
Steffan Noe Christiansen |
title |
Differential Methylation in the <i>GSTT1</i> Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy |
title_short |
Differential Methylation in the <i>GSTT1</i> Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy |
title_full |
Differential Methylation in the <i>GSTT1</i> Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy |
title_fullStr |
Differential Methylation in the <i>GSTT1</i> Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy |
title_full_unstemmed |
Differential Methylation in the <i>GSTT1</i> Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy |
title_sort |
differential methylation in the <i>gstt1</i> regulatory region in sudden unexplained death and sudden unexpected death in epilepsy |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-03-01 |
description |
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 <i>GSTT1</i> 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. |
topic |
epigenetics genetics DNA methylation RNA molecular autopsy sudden cardiac death |
url |
https://www.mdpi.com/1422-0067/22/6/2790 |
work_keys_str_mv |
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