Blood DNA methylation pattern is altered in mesial temporal lobe epilepsy

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.

High-Throughput Data of Circular RNA Profiles in Human Temporal Cortex Tissue Reveals Novel Insights into Temporal Lobe Epilepsy

“…Synaptic reorganisation of mossy fibre projections of the TLE hippocampus plays a significant role in persistent cellular hyperexcitability in the epileptic circuitry of the hippocampal formation [29]. Furthermore, the miRNA-targeting gene chloride channel 6 (CLCN6) is a family member of chloride channels (CLCs) associated with a multitude of physiologic processes involved in electrical excitability, transepithelial transport, electroneutrality, and ionic homeostasis [47]; CLCN6 is also altered in mesial TLE blood samples [48]. In the circ-DROSHA-targeting miRNA network, miR-1252-5p was selected due to the highest scores in this network; its target gene, the alpha 2 subunit of Na + , K + -ATPase (ATP1A2), has a strong relationship with epilepsy [49].…”

CpG methylation signature defines human temporal lobe epilepsy and predicts drug‐resistant

“…Whole blood DNA extraction and quality control were constructed as in our previous study. 28 All samples passed the Illumina quality control. Methylation at individual CpG was reported as a methylation β-value, ranging continuously from 0 (unmethylated) to 1 (completely methylated).…”

Epigenome-wide association study of seizures in childhood and adolescence

“…Mesial temporal lobe epilepsy is one of the most common and most studied forms of epilepsy [13]. A recent study comparing blood DNA methylation in 30 adult patients with mesial temporal lobe epilepsy and 30 controls identified 216 differentially methylated sites between the two groups, including sites on genes involved in ion binding and metabolic activity [14]. DNA methylation differences have also been observed in lymphoblastoid cell lines derived from epileptic patients, both when DNA methylation was measured globally using antibody capture and in the BRD2 gene promoter [15].…”