Torres Carolina Machado, Siebert Marina, Bock Hugo, Mota Suelen Mandelli, Krammer Bárbara Reis, Duarte Juliana Ávila, Bragatti José Augusto, Castan Juliana Unis, de Castro Luiza Amaral, Saraiva-Pereira Maria Luiza, Bianchin Marino Muxfeldt
Graduate Program in Medical Science, Universidade Federal do Rio Grande do Sul, Brazil; Basic Research and Advanced Investigations in Neurology (BRAIN), Experimental Research Centre, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil; Centro de Tratamento de Epilepsia Refratária (CETER), Hospital de Clínicas de Porto Alegre, Brazil; Division of Neurology, Hospital de Clínicas de Porto Alegre, Brazil.
Laboratory of Genetic Identification, Experimental Research Centre, Hospital de Clinicas de Porto Alegre, Brazil.
Epilepsy Res. 2017 Nov;137:1-8. doi: 10.1016/j.eplepsyres.2017.08.010. Epub 2017 Aug 25.
The NTRK2 gene encodes a member of the neurotrophic tyrosine kinase receptor family known as TrkB. It is a membrane-associated receptor with signaling and cellular differentiation properties that has been involved in neuropsychiatric disorders, including epilepsy. We report here the frequencies of NTRK2 allele variants in patients with temporal lobe epilepsy (TLE) compared to controls without epilepsy and explore the impact of these polymorphisms on major clinical variables in TLE.
A case-control study comparing the frequencies of the NTRK2 gene polymorphisms beween 198 TLE Caucasian patients and 200 matching controls without epilepsy. In a second step, the impact of allelic variation on major clinical and electroencephalographic epilepsy variables was evaluated in the group of TLE patients. The following polymorphisms were determined by testing different regions of the NTRK2 gene: rs1867283, rs10868235, rs1147198, rs11140800, rs1187286, rs2289656, rs1624327, rs1443445, rs3780645, and rs2378672. To correct for multiple correlations the level of significance was set at p<0.01.
Patients with TLE showed a statistical trend for increase of the T/T genotype in rs10868235 compared to control (O.R.=1.90; 95%CI=1.17-3.09; p=0.01). Homozygous patients for the A allele in rs1443445 had earlier mean age at onset of seizures, p=0.009 (mean age of 16.6 versus 22.4years). We also observed that the T allele in rs3780645 was more frequent in patients who needed polytheraphy for seizure control than in patients on monotherapy, (O.R.=4.13; 95%CI=1.68-10.29; p=0.001). This finding may reflect an increased difficulty to obtain seizure control in this group of patients. No additional differences were observed in this study.
Patients with epilepsy showed a trend for a difference in rs10868235 allelic distribution compared to controls without epilepsy. NTRK2 variability influenced age at seizure onset and the pharmacological response to seizure control. As far as we know, this is the first study showing an association between NTKR2 allelic variants in human epilepsy. We believe that further studies in this venue will shade some light on the molecular mechanisms involved in epileptogenesis and in the clinical characteristics of epilepsy.
NTRK2基因编码神经营养性酪氨酸激酶受体家族的一员，即TrkB。它是一种具有信号传导和细胞分化特性的膜相关受体，与包括癫痫在内的神经精神疾病有关。我们在此报告颞叶癫痫（TLE）患者与无癫痫对照者中NTRK2等位基因变体的频率，并探讨这些多态性对TLE主要临床变量的影响。
一项病例对照研究，比较198例白种人TLE患者和200例匹配的无癫痫对照者中NTRK2基因多态性的频率。第二步，在TLE患者组中评估等位基因变异对主要临床和脑电图癫痫变量的影响。通过检测NTRK2基因的不同区域确定以下多态性：rs1867283、rs10868235、rs1147198、rs11140800、rs1187286、rs2289656、rs1624327、rs1443445、rs3780645和rs2378672。为校正多重相关性，将显著性水平设定为p<0.01。
与对照组相比，TLE患者中rs10868235的T/T基因型有增加的统计学趋势（O.R.=1.90；95%CI=1.17-3.09；p=0.01）。rs1443445中A等位基因的纯合患者癫痫发作起始的平均年龄较早，p=0.009（平均年龄为16.6岁对22.4岁）。我们还观察到，与单药治疗的患者相比，需要联合治疗来控制癫痫发作的患者中rs3780645的T等位基因更常见（O.R.=4.13；95%CI=1.68-10.29；p=0.001）。这一发现可能反映了该组患者在获得癫痫控制方面增加的难度。本研究未观察到其他差异。
与无癫痫的对照组相比，癫痫患者在rs10868235等位基因分布上存在差异趋势。NTRK2变异性影响癫痫发作起始年龄和癫痫控制的药物反应。据我们所知，这是第一项显示人类癫痫中NTKR2等位基因变体之间存在关联的研究。我们相信，在这一领域的进一步研究将有助于阐明癫痫发生的分子机制和癫痫的临床特征。
