TY - JOUR
T1 - Differential methylation in the GSTT1 regulatory region in sudden unexplained death and sudden unexpected death in epilepsy
AU - Christiansen, Steffan Noe
AU - Jacobsen, Stine Bøttcher
AU - Andersen, Jeppe Dyrberg
AU - Kampmann, Marie Louise
AU - Trudsø, Linea Christine
AU - Olsen, Kristine Boisen
AU - Tfelt-Hansen, Jacob
AU - Banner, Jytte
AU - Morling, Niels
PY - 2021/3/2
Y1 - 2021/3/2
N2 - 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.
AB - 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.
KW - DNA methylation
KW - Epigenetics
KW - Genetics
KW - Molecular autopsy
KW - RNA
KW - Sudden cardiac death
KW - Sudden unexpected death in epilepsy
KW - Sudden unexplained death
U2 - 10.3390/ijms22062790
DO - 10.3390/ijms22062790
M3 - Journal article
C2 - 33801838
AN - SCOPUS:85102122295
VL - 22
JO - International Journal of Molecular Sciences (CD-ROM)
JF - International Journal of Molecular Sciences (CD-ROM)
SN - 1424-6783
IS - 6
M1 - 2790
ER -