NTRK2 (TrkB gene) variants and temporal lobe epilepsy: A genetic association study

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.