Abstract
BackgroundEpigenetics underlying refractory epilepsy is poorly understood. DNA methylation may affect gene expression in epilepsy patients without affecting DNA sequences. Herein, we investigated the association between Carbamazepine-resistant (CBZ-resistant) epilepsy and EPHX1 methylation in a northern Han Chinese population, and conducted an analysis of clinical risk factors for CBZ-resistant epilepsy.MethodsSeventy-five northern Han Chinese patients participated in this research. 25 cases were CBZ-resistant epilepsy, 25 cases were CBZ-sensitive epilepsy and the remaining 25 cases were controls. Using a CpG searcher was to make a prediction of CpG islands; bisulfite sequencing PCR (BSP) was applied to test the methylation of EPHX1. We then did statistical analysis between clinical parameters and EPHX1 methylation.ResultsThere was no difference between CBZ-resistant patients, CBZ-sensitive patients and healthy controls in matched age and gender. However, a significant difference of methylation levels located in NC_000001.11 (225,806,929.....225807108) of the EPHX1 promoter was found in CBZ-resistant patients, which was much higher than CBZ-sensitive and controls. Additionally, there was a significant positive correlation between seizure frequency, disease course and EPHX1 methylation in CBZ-resistant group.ConclusionMethylation levels in EPHX1 promoter associated with CBZ-resistant epilepsy significantly. EPHX1 methylation may be the potential marker for CBZ resistance prior to the CBZ therapy and potential target for treatments.
Highlights
Epigenetics underlying refractory epilepsy is poorly understood
Microsomal Epoxide Hydrolase (EPHX1) methylation may be the potential marker for common DNA methylation usually happensCarbamazepine (CBZ) resistance prior to the CBZ therapy and potential target for treatments
Clinical parameter evaluation The clinical characteristics, EPHX1 methylation distribution between different groups were shown in Tables 1 and 2 respectively
Summary
Epigenetics underlying refractory epilepsy is poorly understood. DNA methylation may affect gene expression in epilepsy patients without affecting DNA sequences. We investigated the association between Carbamazepine-resistant (CBZ-resistant) epilepsy and EPHX1 methylation in a northern Han Chinese population, and conducted an analysis of clinical risk factors for CBZ-resistant epilepsy. According to international League Against Epilepsy (ILAE), about 65 millions of epilepsy people have been reported in the world [1], and approximately 36% of epilepsy patients have poor or no drug-response [2]. Epigenetic modification means genomic reprogramming without affecting DNA sequence, such as microRNA expression, histone modification, and especially DNA methylation [3, 4]. About 30–40% of epilepsy patients were CBZ-resistant according to the recent studies [8, 9]. Among Cytochrome P450 proteins (CYP), the CYP3A4 or CYP2C8 palys an important role in the the
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