Blood DNA methylation pattern is altered in mesial temporal lobe epilepsy.
Blood DNA methylation pattern is altered in mesial temporal lobe epilepsy.
复制标题
内侧颞叶癫痫患者血液 DNA 甲基化模式发生改变
DOI：
10.1038/srep43810
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发表时间：
2017-03-09
影响因子：
4.6
通讯作者：
Xiao B
中科院分区：
文献类型：
--
作者：
Long HY;Feng L;Kang J;Luo ZH;Xiao WB;Long LL;Yan XX;Zhou L;Xiao B
内侧颞叶癫痫（MTLE）是一种常见的癫痫性疾病，其是否与外周表观遗传学改变有关尚不清楚。在这里，我们比较了MTLE患者（n = 30）相对于对照组（n = 30）的血液全基因组DNA甲基化模式与人类甲基化450 K微珠芯片测定，并探索基因和通路，差异甲基化使用生物信息学分析。MTLE组和对照组在216个位点的DNA甲基化存在显著差异（P < 1.03e-07），其中164个位点涉及高甲基化，52个位点涉及低甲基化。两个高和32低甲基化位点与启动子相关，而87高和43低甲基化位点对应于编码区。差异甲基化的基因主要与预测参与阴离子结合、氧化还原活性、生长调节、骨骼发育和药物代谢的途径相关，最不同的基因包括SLC 34 A2、CLCN 6、CLCA 4、CYP 3A 43、CYP 3A 4和CYP 2C 9。在MTLE患者中，相对于疾病持续时间、抗癫痫药抗性和海马硬化的MRI改变，基因组也出现差异甲基化。在MTLE中观察到的外周表观遗传变化可能参与某些疾病相关的调节，并需要进一步的翻译研究。
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.