PMID- 34393975 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211217 IS - 1664-2295 (Print) IS - 1664-2295 (Electronic) IS - 1664-2295 (Linking) VI - 12 DP - 2021 TI - DNA Methylation Signature of Epileptic Encephalopathy-Related Pathogenic Genes Encoding Ion Channels in Temporal Lobe Epilepsy. PG - 692412 LID - 10.3389/fneur.2021.692412 [doi] LID - 692412 AB - Epilepsy is characterized by highly abnormal synchronous discharge of brain neurons, and ion channels are fundamental in the generation and modulation of neural excitability. Considering that abnormal methylation can either activate or repress genes, this study was designed to explore the DNA methylation signature of pathogenic genes encoding ion channels in temporal lobe epilepsy (TLE). In total, 38 TLE patients and 38 healthy controls were enrolled in the study, and genomic DNA and total protein of the lymphocytes were extracted from peripheral blood samples to assess methylation and protein levels. The DNA methylation levels of all 12 genes examined were significantly lower in the TLE group than in the control group. After false-positive correction, 83.3% (10/12) of these genes, namely, gamma-aminobutyric acid type A receptor subunit beta1 (GABRB1), gamma-aminobutyric acid type A receptor subunit beta2 (GABRB2), gamma-aminobutyric acid type A receptor subunit beta1 (GABRB3), glutamate ionotropic receptor NMDA type subunit 1 (GRIN1), glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A), glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B), hyperpolarization activated cyclic nucleotide gated potassium channel 1 (HCN1), potassium voltage-gated channel subfamily A member 2 (KCNA2), potassium voltage-gated channel subfamily B member 1 (KCNB1), and potassium sodium-activated channel subfamily T member 1 (KCNT1), were still differentially expressed. Among these ion channels, HCN1 and KCNA2 were selected to evaluate the effects of DNA methylation, and the levels of these proteins were inversely upregulated in the TLE group compared to the control group. As the genes identified as having differential methylation levels are involved in both excitatory and inhibitory ion channels, this study observed by binary logistic regression that hypermethylated GARAB1 was an independent risk factor for TLE, indicating that the overwhelming effect of ion channels on TLE is probably inhibitory from the perspective of DNA methylation. All these findings support the involvement of DNA methylation in TLE pathologies, but the mechanisms need to be further investigated. CI - Copyright (c) 2021 Tao, Chen, Wu, Chen, Chen, Fu, Sun, Zhou, Zhong, Zhou and Li. FAU - Tao, Hua AU - Tao H AD - Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. AD - Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Chen, Zengqiang AU - Chen Z AD - Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Wu, Jianhao AU - Wu J AD - Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Chen, Jun AU - Chen J AD - Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Chen, Yusen AU - Chen Y AD - Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Fu, Jiawu AU - Fu J AD - Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Sun, Chaowen AU - Sun C AD - Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Zhou, Haihong AU - Zhou H AD - Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Zhong, Wangtao AU - Zhong W AD - Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Zhou, Xu AU - Zhou X AD - Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. AD - Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Li, Keshen AU - Li K AD - Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. AD - Neurology & Neurosurgery Division, Stroke Center, Clinical Medicine Research Institute & The First Affiliated Hospital, Jinan University, Guangzhou, China. LA - eng PT - Journal Article DEP - 20210729 PL - Switzerland TA - Front Neurol JT - Frontiers in neurology JID - 101546899 PMC - PMC8358672 OTO - NOTNLM OT - DNA methylation OT - epigenetic OT - genetic susceptibility OT - ion channels OT - temporal lobe epilepsy COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/08/17 06:00 MHDA- 2021/08/17 06:01 PMCR- 2021/07/29 CRDT- 2021/08/16 05:48 PHST- 2021/04/08 00:00 [received] PHST- 2021/06/23 00:00 [accepted] PHST- 2021/08/16 05:48 [entrez] PHST- 2021/08/17 06:00 [pubmed] PHST- 2021/08/17 06:01 [medline] PHST- 2021/07/29 00:00 [pmc-release] AID - 10.3389/fneur.2021.692412 [doi] PST - epublish SO - Front Neurol. 2021 Jul 29;12:692412. doi: 10.3389/fneur.2021.692412. eCollection 2021.