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Epilepsy Res. 2014 Oct;108(8):1267-73. doi: 10.1016/j.eplepsyres.2014.07.001. Epub 2014 Jul 18.

Association of GABRA6 1519 T>C (rs3219151) and Synapsin II (rs37733634) gene polymorphisms with the development of idiopathic generalized epilepsy.

Author information

1
Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad 500016, India; Dr. NTR University of Health Sciences, Vijayawada 500008, Andhra Pradesh, India.
2
Dr. Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation, Gannavaram, Andhra Pradesh, India.
3
Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, India.
4
Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad 500016, India.
5
Centre for Human Genetics, Central University of Punjab, Bathinda 151001, Punjab, India. Electronic address: anjanadurani@yahoo.co.in.

Abstract

The idiopathic generalized epilepsy (IGE) is a neurological disorder which accounts for approximately 30% of all epilepsy cases. Patients identified with IGE syndromes have pharmacoresponsive epilepsies without abnormal neurological symptoms, structural brain lesions and are of unknown origin. A genetic etiology to IGEs has been proposed. Gamma amino butyric acid (GABA), a major inhibitory neurotransmitter acts by binding to transmembrane GABAA and GABAB receptors of both pre- and postsynaptic neurons. Synapsin II (SynII), a neuron specific phosphoprotein plays a major role in synaptogenesis and neurotransmitter release. The present study was carried out with an aim to evaluate the association of GABRA6 (rs3219151) T>C and Syn II (rs37733634) A>G gene polymorphisms with IGE. Molecular analysis revealed that the frequency of 'CC' genotype and 'C'allele of GABRA6 (rs3219151) T>C gene polymorphism was significantly higher in IGE patients compared to healthy controls [CC vs. TT, χ2=26; p<0.001; Odds ratio=3.6 (95% CI; 2.1-5.9); C vs T, χ2=24.7; p<0.001; Odds ratio=1.78 (95% CI; 1.4-2.2)]. The frequency of 'GG' genotype and 'G' allele of the intronic polymorphism A>G in Syn II gene was also found to be significantly associated with the disease when compared to controls [GG vs AA, χ2=64.52; p<0.001; Odds ratio=7.37 (95% CI; 4.4-12.3); G vs. A, χ2=65.78; p<0.001; Odds ratio=2.57 (95% CI; 2.0-3.2)]. The generalized multifactor dimensionality reduction method was employed to detect gene-gene interactions. The gene-gene interaction at two loci involving GABRA6 and Syn II revealed a significant association [χ2=36.6, p<0.001, Odds ratio=3.17 (95% CI; 2.2-4.6)] with IGE. Therefore, the present study clearly indicates that both GABRA6 (rs3219151) T>C and Syn II (rs37733634) A>G polymorphisms are important risk factors for the development of IGE in the South Indian population from Andhra Pradesh. The gene-gene interaction studies demonstrated significant interactive effects of these two loci in the development of the disease.

KEYWORDS:

Epileptogenesis; Gamma-amino butyric acid (GABA); Gene–gene interaction; Idiopathic generalized epilepsies; Neurotransmitter; Synapsin II

[Indexed for MEDLINE]

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