The purpose of the present study was to investigate the possible association between temporal lobe epilepsy and NRG1 gene polymorphisms. A total of 73 patients and 69 controls were involved in this study. Genomic DNAs from the patients and controls were genotyped by polymerase chain reaction-ligase detection reaction method. There was an association of rs35753505 (T>C) with temporal lobe epilepsy (χ2 = 6.730, P = .035). The frequency of risk allele C of rs35753505 was significantly higher (69.9%) in patients compared to controls (55.8%) (χ2 = 6.023, P = .014). Interestingly, the significant difference of NRG1 genotype and allele frequency only existed among males, but not females. In addition, no statistically significant association was found between rs6994992, rs62510682 polymorphisms, and temporal lobe epilepsy. These data indicate that rs35753505 of NRG1 plays an important role in conferring susceptibility to the temporal lobe epilepsy in a Chinese Han population.
HildebrandMSDahlHHDamianoJA. Recent advances in the molecular genetics of epilepsy. J Med Genet. 2013;50:271–279.
4.
ThomasRHBerkovicSF. The hidden genetics of epilepsy—a clinically important new paradigm. Nat Rev Neurol. 2014;10:283–292.
5.
MeiLNaveKA. Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases. Neuron. 2014;83:27–49.
6.
WenLLuYSZhuXH. Neuregulin 1 regulates pyramidal neuron activity via ErbB4 in parvalbumin-positive interneurons. Proc Natl Acad Sci U S A. 2010;107:1211–1216.
7.
EilamRPinkas-KramarskiRRatzkinBJ. Activity-dependent regulation of Neu differentiation factor/neuregulin expression in rat brain. Proc Natl Acad Sci U S A. 1998;95:1888–1893.
8.
OzakiMItohKMiyakawaY. Protein processing and releases of neuregulin-1 are regulated in an activity-dependent manner. J Neurochem. 2004;91:176–188.
9.
CascellaNGSchretlenDJSawaA. Schizophrenia and epilepsy: is there a shared susceptibility?Neurosci Res. 2009;63:227–235.
10.
DengCPanBEngelM. Neuregulin-1 signalling and antipsychotic treatment: potential therapeutic targets in a schizophrenia candidate signalling pathway. Psychopharmacology. 2013;226:201–215.
11.
LiKXLuYMXuZH. Neuregulin 1 regulates excitability of fast-spiking neurons through Kv1.1 and acts in epilepsy. Nat Neurosci. 2012;15:267–273.
12.
TanGHLiuYYHuXL. Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons. Nat Neurosci. 2012;15:258–266.
13.
Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia. 1989;30:389–399.
14.
BobPPalusMSustaM. Sensitization, epileptic-like symptoms and local synchronization in patients with paranoid schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:143–146.
15.
QinPXuHLaursenTM. Risk for schizophrenia and schizophrenia-like psychosis among patients with epilepsy: population based cohort study. BMJ. 2005;331:23.
16.
DedeurwaerdereSBoetsSJanssensP. In the grey zone between epilepsy and schizophrenia: alterations in group II metabotropic glutamate receptors. Acta Neurol Belg. 20141225.
17.
SchmittAKoschelJZinkM. Gene expression of NMDA receptor subunits in the cerebellum of elderly patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2010;260:101–111.
18.
AminiERezaeiMMohamed IbrahimN. A molecular approach to epilepsy management: from current therapeutic methods to preconditioning efforts. Mol Neurobiol. 201499.
19.
HansenKBMullasserilPDawitS. Implementation of a fluorescence-based screening assay identifies histamine H3 receptor antagonists clobenpropit and iodophenpropit as subunit-selective N-methyl-d-aspartate receptor antagonists. J Pharmacol Exp Ther. 2010;333:650–662.
20.
ModdelGJacobsonBYingZ. The NMDA receptor NR2B subunit contributes to epileptogenesis in human cortical dysplasia. Brain Res. 2005;1046:10–23.
21.
YenWWilliamsonJBertramEH. A comparison of three NMDA receptor antagonists in the treatment of prolonged status epilepticus. Epilepsy Res. 2004;59:43–50.
22.
HanadaTHashizumeYTokuharaN. Perampanel: a novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy. Epilepsia. 2011;2:1331–1340.
23.
BartonMESteve WhiteH. The effect of CGX-1007 and CI-1041, novel NMDA receptor antagonists, on kindling acquisition and expression. Epilepsy Res. 2004; 59:1–12.
BennettM. Positive and negative symptoms in schizophrenia: the NMDA receptor hypofunction hypothesis, neuregulin/ErbB4 and synapse regression. Aust NZ Psychiat. 2009;43:711–721.
26.
KotsopoulosIAvan MerodeTKesselsFG. Systematic review and meta-analysis of incidence studies of epilepsy and unprovoked seizures. Epilepsia. 2002;43:1402–1409.
MiyagawaSKatsuYWatanabeH. Estrogen-independent activation of erbBs signaling and estrogen receptor alpha in the mouse vagina exposed neonatally to diethylstilbestrol. Oncogene. 2004;23:340–349.
29.
Lacroix-FralishMLTawfikVLNutile-McMenemyN. Neuregulin 1 is a pronociceptive cytokine that is regulated by progesterone in the spinal cord: implications for sex specific pain modulation. Eur J Pain. 2008;12:94–103.
30.
LiDCollierDAHeL. Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia. Hum Mol Genet. 2006;15:1995–2002.
31.
PrataDPBreenGOsborneS. An association study of the neuregulin 1 gene, bipolar affective disorder and psychosis. Psychiatr Genet. 2009;19:113–116.
32.
MoonERollinsBMesenA. Lack of association to a NRG1 missense polymorphism in schizophrenia or bipolar disorder in a Costa Rican population. Schizophr Res. 2011;131:52–57.
33.
PatersonCWangYKleinmanJELawAJ. Effects of schizophrenia risk variation in the NRG1 gene on NRG1-IV splicing during fetal and early postnatal human neocortical development. Am J Psychiatry. 2014;171:979–989.
34.
FazzariPPaternainAVValienteM. Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling. Nature. 2010;464:1376–1380.
IyengarSSMottDD. Neuregulin blocks synaptic strengthening after epileptiform activity in the rat hippocampus. Brain Res. 2008;1208:67–73.
37.
BackxLCeulemansBVermeeschJR. Early myoclonic encephalopathy caused by a disruption of the neuregulin-1 receptor ErbB4. Eur J Hum Genet. 2009;17:378–382.
38.
DaiAIAkcaliAKoskaS. Contribution of KCNJ10 gene polymorphisms in childhood epilepsy. J Child Neurol. 2014;30:296–300.
