Department of Neurology, Rikshospitalet University Hospital, Oslo, Norway.
Epilepsy Res. 2010 Jan;88(1):55-64. doi: 10.1016/j.eplepsyres.2009.09.023. Epub 2009 Oct 28.
The etiopathogenesis of temporal lobe epilepsy (TLE) and its subgroups - mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and TLE with antecedent febrile seizures (TLE-FS) - is poorly understood. It has been proposed that the water channel aquaporin-4 (AQP4) and the potassium channel Kir4.1 (KCNJ10 gene) act in concert to regulate extracellular K(+) homeostasis and that functional alterations of these channels influence neuronal excitability. The current study was designed to identify variants of the AQP4 and KCNJ10 genes associated with TLE and subgroups of this condition.
We included 218 Norwegian patients with TLE and 181 ethnically matched healthy controls. An association study was established in which all TLE patients were compared with healthy controls. Additionally, subgroups of 56 MTLE-HS patients were compared with 162 TLE patients without HS, and 102 TLE-FS patients were compared with 105 TLE without FS.
We found eight single SNPs, seven in KCNJ10 and one between KCNJ10 and KCNJ9, associated with TLE-FS (nominal p-values from 0.009 to 0.041). Seven of the SNPs segregate into one large haplotype block expanding from KCNJ10 to KCNJ9, including the region interposed those genes. One haplotype was overrepresented in the TLE-FS cases (nominal p-value 0.014). These results were confirmed by explorative multivariate analysis indicating that a combination of SNPs from KCNJ10, the region between KCNJ10 and KCNJ9, and the AQP4 gene is associated with TLE-FS. For the TLE cohort as a whole, explorative multivariate analysis indicated a combination of SNPs from the KCNJ10 and AQP4 genes in association with TLE.
Variations in the AQP4 and the KCNJ10/KCNJ9 region are likely to be associated with TLE, particularly TLE-FS, supporting the suggestion that perturbations of water and K(+) transport are involved in the etiopathogenesis of TLE.
颞叶癫痫（TLE）及其亚组 - 伴有海马硬化的内侧颞叶癫痫（MTLE-HS）和伴有热性惊厥病史的 TLE（TLE-FS）的发病机制尚不清楚。有人提出水通道 Aquaporin-4（AQP4）和钾通道 Kir4.1（KCNJ10 基因）协同作用以调节细胞外 K+稳态，并且这些通道的功能改变会影响神经元兴奋性。本研究旨在确定与 TLE 及其亚组相关的 AQP4 和 KCNJ10 基因的变异。
我们纳入了 218 名挪威 TLE 患者和 181 名与之匹配的健康对照者。建立了一项关联研究，其中将所有 TLE 患者与健康对照者进行比较。此外，将 56 名 MTLE-HS 患者亚组与 162 名无 HS 的 TLE 患者和 102 名 TLE-FS 患者与 105 名无 FS 的 TLE 患者进行比较。
我们发现了八个单核苷酸多态性（SNP），其中七个位于 KCNJ10 基因中，一个位于 KCNJ10 和 KCNJ9 之间，与 TLE-FS 相关（名义 p 值从 0.009 到 0.041）。七个 SNP 可分为一个从 KCNJ10 到 KCNJ9 的大片段单倍型块，包括插入这些基因之间的区域。一个单倍型在 TLE-FS 病例中过度表达（名义 p 值 0.014）。这些结果通过探索性多变量分析得到了证实，该分析表明 KCNJ10、KCNJ10 与 KCNJ9 之间的区域以及 AQP4 基因的 SNP 组合与 TLE-FS 相关。对于整个 TLE 队列，探索性多变量分析表明 KCNJ10 和 AQP4 基因的 SNP 组合与 TLE 相关。
AQP4 和 KCNJ10/KCNJ9 区域的变异可能与 TLE 特别是 TLE-FS 相关，支持水和 K+转运的扰动参与 TLE 的发病机制的观点。
