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Hypomethylation of LINE-1 elements in schizophrenia and bipolar disorder.
Journal of Psychiatric Research 2018 October 11
Schizophrenia (SCZ) and bipolar disorder (BPD) are severe mental illnesses with evidence of significant genetic and environmental etiological elements in their complex etiologies. 5'-Methylcytosine is the main epigenetic DNA modification that mediates the interplay between genetic and environmental components. In humans, most 5'-methylcytosine modifications are observed in CpG-rich regions within the long interspersed nuclear element (LINE-1). LINE-1 is a mobile retrotransposon that comprises ∼17% of the human genome, and its methylation levels are highly correlated with global DNA methylation levels. LINE-1 insertions are also reported to be mental illnesses-associated genomic risk factors. To examine the LINE-1 methylation levels in SCZ and BPD, this study employed a bisulfite conversion-specific one-label extension (BS-OLE) method to detect the methylation levels at three CpG sites (S1, S2 and S3) of LINE-1 in peripheral blood DNA from a Han Chinese cohort composed of 92 SCZ patients, 99 BPD patients and 92 controls (CON). The results showed a decreased S1 methylation level in SCZ, decreased S2 methylation level in BPD and decreased S3 methylation levels in both SCZ and BPD relative to those of the CON. A female-dependent positive correlation of the S3 methylation level with age in CON became non-significant in both SCZ and BPD. These findings demonstrated that LINE-1 methylation varied with development and disease status. The roles of LINE-1 methylation in the pathogenesis of SCZ and BPD remain to be elucidated.
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