Differential Methylation in the GSTT1 Regulatory Region in Sudden Unexplained Death and Sudden Unexpected Death in Epilepsy.
Int J Mol Sci
; 22(6)2021 Mar 10.
Article
em En
| MEDLINE
| ID: mdl-33801838
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sequências Reguladoras de Ácido Nucleico
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Morte Súbita Cardíaca
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Metilação de DNA
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Predisposição Genética para Doença
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Morte Súbita Inesperada na Epilepsia
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Glutationa Transferase
Limite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
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Middle aged
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Newborn
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Dinamarca