LACK OF ASSOCIATION BETWEEN CHRNA4 C.651 C>T GENE POLYMORPHISM AND GENETIC GENERALIZED EPILEPSY

Abstract

Background: The neuronal nicotinic acetylcholine receptor (nAChR) channels become more sensitive to acetylcholine due to mutations of CHRNA4 gene, thereby channels open more easily resulting in ion flow across the cell membrane that leads to changes in signaling between neurons. The variants of the CHRNA4 gene have been associated with several psychiatric and brain disorders including autosomal dominant nocturnal frontal lobe epilepsy. Aim: The present study was aimed to evaluate the possible association of CHRNA4 c.651 C>T gene polymorphism with genetic generalized epilepsy (GGE). Methods: The genotyping of CHRNA4 gene polymorphism was performed using PCR-RFLP assay. Results: In majority patients, GGE onset was <18 years (185 patients 61.6%) and remaining 115 patients (38.3%) had the onset above 18 years. The absence seizure and epilepsy type were predominantly seen in patients with <18 years age group (36.4% and 28.1% respectively) compared to >18 years group (2.6% and 6.08 respectively). However, the myoclonus seizures were more predominantly seen in patients with >18 years age group (80%) compared to < 18 years group (7.2%). Significant variation was observed with the frequency of tonic-clonic type seizures in <18 year age group as compared to >18 years group. The molecular analysis revealed no significant difference in the genotypic distribution as well as allelic frequency between patients and controls (p>0.05). The genotypes, CT and TT were not observed in controls [(TT vs. CC, χ2=0.3; p=0.30; T vs C, χ2 = 17.23; p <0.05)]. Conclusion: No significant association was found between CHRNA4 c.651 C>T gene polymorphism with IGE in the South Indian population.