Increased CPA6 promoter methylation in focal epilepsy and in febrile seizures
Increased CPA6 promoter methylation in focal epilepsy and in febrile seizures
复制标题
DOI：
10.1016/j.eplepsyres.2013.10.007
复制
发表时间：
2014-01-01
影响因子：
2.2
通讯作者：
Salzmann, A.
中科院分区：
文献类型：
--
作者：
Belhedi, N.;Perroud, N.;Salzmann, A.
局灶性癫痫（FE）是成人癫痫最常见的形式之一，通常被认为是一种多因素疾病。发热性癫痫（FS）通常出现在儿童期FE患者的一个亚型，即颞叶癫痫（TLE）和海马硬化（HS）。FS是与发热相关的最常见的人类惊厥事件。FS的遗传证据表明其遗传模式复杂。到目前为止，为了在基因组水平上研究基因，已经进行了家族形式的连锁分析和关联研究，但没有确凿的证据表明FE和FS有明确的关系。作为一种复杂的疾病，环境因素可能通过对关键候选基因（如编码胞外蛋白羧基肽酶A6的CPA6）的表观遗传修饰起着至关重要的作用。因此，我们评估了CPA6启动子的DNA甲基化。在186名FE患者和92名FS患者中，与93名健康对照和42名使用抗癫痫药物（aed）治疗的对照相比，我们发现癫痫患者的甲基化水平明显更高。FE患者的甲基化水平为3.4% (+/- 3.2%)，FS患者的甲基化水平为4.3%(+/- 3.5%)，而健康个体和接受aed治疗的对照组的甲基化水平分别为0.8%（+/- 2.9%）和1.5% （+/- 3.9%）
Focal epilepsy (FE) is one of the most common forms of adult epilepsy and is usually regarded as a multifactorial disorder. Febrile seizures (FS) often appear during childhood in a subtype of FE patients, i.e. with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). FS are the most common human convulsive event associated with fever. Genetic evidences for FS have suggested a complex mode of inheritance. Until now, to investigate genes at the genomic level, linkage analysis of familial forms and association studies have been performed, but nothing conclusive has been clearly related to FE and FS. As complex disorders, environmental factors might play a crucial role through epigenetic modification of key candidate genes such as CPA6, which encodes Carboxypeptidase A6, an extracellular protein. Therefore, we assessed DNA methylation in promoter of CPA6. In 186 FE patients and 92 FS patients compared to 93 healthy controls and 42 treated controls with antiepileptic drugs (AEDs), we found significant higher levels of methylation for epileptic patients. Methylation status were 3.4% (+/- 3.2%) for FE cases and 4.3% (+/- 3.5%) for FS cases, whereas healthy individuals and treated controls with AEDs showed a level of 0.8% (+/- 2.9%) and 1.5% (+/- 3.9%), respectively (p