Altered ANRIL Methylation in Epileptic Patients.

Abstract

Long non-coding RNAs (lncRNAs) have regulatory roles in several aspects of cellular physiology. Recent studies have also revealed their role in neuronal differentiation and the pathophysiology of neurologic disorders such as epilepsy. We have recently reported altered expression of a number of lncRNAs in the peripheral blood of epileptic patients in association with their response to antiepileptic drugs. One the most significantly altered lncRNAs in epileptic patients is the antisense non-coding RNA in the INK4 locus (ANRIL), whose expression has been found to be higher in both refractory and non-refractory groups compared with controls. In the current study, we aimed to identify the methylation status of this lncRNA to suggest a potential mechanism for deregulated ANRIL expression. Thus, we assessed the methylation status of the ANRIL promoter in 40 patients with refractory epilepsy, 40 patients with non-refractory epilepsy and 40 normal controls using the high-resolution melting (HRM) method. The HRM results showed hypomethylation of the ANRIL promoter region in both refractory epilepsy and non-refractory epilepsy patients compared with normal controls. This methylation pattern was consistent with the recently reported upregulation of this lncRNA in patients with epilepsy. Thus, we suggest altered methylation of the ANRIL promoter as a potential cause of its aberrant expression in peripheral blood of epileptic patients.