Association of intronic polymorphism rs3773364 A>G in synapsin‐2 gene with idiopathic epilepsy

Abstract

In epilepsy, there is a tendency towards recurrent unprovoked seizures. Seizures result due to the excessive electrical misfiring in the brain between neurons and disturbance in neurotransmitter release. Several gene products affect the behavior of these neurons by regulating neurotransmission via several mechanisms. One such gene, Synapsin-2 (SYN2), involved in synaptogenesis is also reported to regulate the neurotransmitter release. We hypothesized that SYN2 gene and its polymorphisms could affect the process of epileptogenesis and therapeutic response in humans. In this hospital-based study, we enrolled 372 patients with epilepsy and 199 control subjects. We selected rs3773364 A>G polymorphism in SYN2 gene and analyzed its distribution in north Indian patients with epilepsy and control subjects. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. According to the results obtained, SYN2 "AG" genotype frequency was significantly higher in patients with epilepsy versus control subjects in north Indian population (P = 0.02, OR = 1.55, 95% CI = 1.06-2.26). After subclassification, we observed higher frequency of AG genotype in idiopathic patients as compared to control subjects (P = 0.01, OR = 1.67, 95% CI = 1.08-2.56). There were no significant differences in genotypic (AG: OR = 0.80, P = 0.377; GG: P = 0.628, OR = 1.17) or allelic (P = 0.86, OR = 1.03) frequency distributions in patients with multiple drug resistance versus patients with drug-responsive epilepsy. Results from our study indicate the involvement of SYN2 gene polymorphism in conferring risk to epilepsy; however, the genetic variant does not seem to modulate drug-response in epilepsy pharmacotherapy.

Protein Expression Dynamics during Postnatal Mouse Brain Development

“…This experimental design enabled the identification of 251 differentially expressed proteins over the course of forebrain development. Numerous neuronal proteins were present in this list of developmentally regulated proteins, including CRMP2,25 CRMP4,25,26 DYN1,27 ENOG,28 4-Aminobutyrate aminotransferase,29 Growth associated protein 43,30 Neurolysin,31 Septin 5,32 and Vdac1 Protein 33. A major part of the mapped proteins are already associated with developmental processes (Supplemental Tables 2, 4), but to our knowledge L-3-hydroxyacyl-coenzyme A dehydrogenase (HAD) and Pyridoxal kinase have not been linked to development.…”

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

“…Most epilepsies have been linked to mutations in voltage-gated channels; however, this is the first time a synaptic vesicle protein has been recognized. Single-nucleotide polymorphisms in the synapsin II gene were found to be associated with sporadic epilepsy (Cavalleri et al, 2007;Lakhan et al, 2010). Postmortem brain studies show significant decreases in synapsin II mRNA in prefrontal cortex of subjects with schizophrenia (Mirnics et al, 2001).…”

Subconvulsant doses of pentylenetetrazol uncover the epileptic phenotype of cultured synapsin-deficient Helix serotonergic neurons in the absence of excitatory and inhibitory inputs

“…The importance of characterizing the excitable phenotype developed by Syn deficiencies is highlighted by the fact that Syn deletion and mutations have been associated with the development of epileptic phenotypes in animals (Li et al, 1995;Rosahl et al, 1995;Gitler et al, 2004;Etholm and Heggelund, 2009;Ketzef et al, 2011;Etholm et al, 2013;Ketzef and Gitler, 2014). In humans, epilepsy and other disorders have been linked to mutations in SynI (Garcia et al, 2004;Fassio et al, 2011b;Lignani et al, 2013;Giannandrea et al, 2013) and SynII genes (Cavalleri et al, 2007;Lakhan et al, 2010;Corradi et al, 2014). In addition, the seizure susceptibility of mice TKO brain slices has been reported to anticipate epileptic phenotypes (Boido et al, 2010;Feliciano et al, 2013).…”