We evaluate possible epigenetic mechanisms in epilepsy, by analyzed methylation changes in promoters I and IV of the BDNF gene in patients with temporal lobe epilepsy (TLE).

Epigenetic is the study of inheritable changes in gene expression that occur with no modifications in the DNA sequence. Methylation can lead to promoter gene silencing or loss of its function. The BDNF gene, a member of the neurotrophin family which encodes brain-derived neurotrophic factor (BDNF) has been implicated in epileptogenesis.

Analysis of 172 patients with TLE and 158 controls for metylation status of promoters I and IV of the BDNF gene of peripheral blood and its correlation with the clinical characteristics of TLE. Methylation profile analysis was performed using the High Resolution Melting (HRM) method on a StepOne™ Real-Time PCR System (Applied Biosystems®). As a methylated/unmethylated control, we used the Cells-to-CpG Methylated and Unmethylated gDNA Control Kit (Applied Biosystems®). Methylated was defined as ratios of methylation of 75% or higher.

Patients showed increased methylation in promoter I (p<0.047) and decreased methylation in promoter IV (p<0.005) when compared with controls. Considering only patients with epilepsy, the methylation frequency of BDNF promoter I was 7.6% (n=13), and of promoter IV was 1.7% (n=3), as opposed to the unmethylated status, in which 92.4% (n=159) of patients showed unmetylated status for BDNF promoter I and 98.3% (n=169) for BDNF promoter IV. There were no statistical differences of promoter methylation status regarding main features of TLE.

We observed differential methylation profiles of BDNF promoters I and IV in patients with temporal lobe epilepsy. Our seminal results may indicate that methylation of selective genes like BDNF gene or other epigenetic mechanisms might be important contributing factors for epileptogenesis or epilepsy characteristics. Therefore, we believe that these mechanisms need to be further explored.