Abstract
Mesial temporal lobe epilepsy (MTLE) is a common epileptic disorder; little is known whether it is associated with peripheral epigenetic changes. Here we compared blood whole genomic DNA methylation pattern in MTLE patients (n = 30) relative to controls (n = 30) with the Human Methylation 450 K BeadChip assay, and explored genes and pathways that were differentially methylated using bioinformatics profiling. The MTLE and control groups showed significantly different (P < 1.03e-07) DNA methylation at 216 sites, with 164 sites involved hyper- and 52 sites hypo- methylation. Two hyper- and 32 hypo-methylated sites were associated with promoters, while 87 hyper- and 43 hypo-methylated sites corresponded to coding regions. The differentially methylated genes were largely related to pathways predicted to participate in anion binding, oxidoreductant activity, growth regulation, skeletal development and drug metabolism, with the most distinct ones included SLC34A2, CLCN6, CLCA4, CYP3A43, CYP3A4 and CYP2C9. Among the MTLE patients, panels of genes also appeared to be differentially methylated relative to disease duration, resistance to anti-epileptics and MRI alterations of hippocampal sclerosis. The peripheral epigenetic changes observed in MTLE could be involved in certain disease-related modulations and warrant further translational investigations.
Highlights
Temporal lobe epilepsy (TLE) is a common neurological disease that may affect up to 1% population, representing a significant healthcare and financial burden to society and families[1,2]
We carried out a case-control study on blood whole-genome DNA methylation pattern in 30 Mesial temporal lobe epilepsy (MTLE) patients relative to sex/age-matched controls, and have identified a panel of differentially methylated genes involved in multiple interactive molecular pathways between the two groups
(1) Staining controls indicated that the signal of dinitrophenyl (DNP) and biotin attached beads was sufficient; (2) Hybridization controls indicated that the signal was intensified with the increase of biotin-tagged fluorescent probes in a concentration-dependent manner; (3) Target removal controls revealed a loss of fluorescent signal in conditions whereby the oligos were extended using the probe sequence as template; (4) Extension controls showed that the signal was enhanced with the extension of either the guanine-cytosine (GC) residues or adenine-thymine (AT) residues (Supplementary Fig. 2)
Summary
Temporal lobe epilepsy (TLE) is a common neurological disease that may affect up to 1% population, representing a significant healthcare and financial burden to society and families[1,2]. Epigenetic changes are being recognized as a part of the molecular reconfiguration in TLE, with a wide array of genes involved in neuronal/synaptic transmission, cell survival/death and transcriptional regulation differentially methylated in the brains of patients[38,39,40,41,42]. We carried out a case-control study on blood whole-genome DNA methylation pattern in 30 MTLE patients relative to sex/age-matched controls, and have identified a panel of differentially methylated genes involved in multiple interactive molecular pathways between the two groups
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