title: Association of GABRA6 1519 T>C (rs3219151) and Synapsin II (rs37733634) gene polymorphisms with the development of idiopathic generalized epilepsy.
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.
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad 500016, India; Dr. NTR University of Health Sciences, Vijayawada 500008, Andhra Pradesh, India.
authors.forename: D K V
authors.initials: DK
authors.lastname: Prasad
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad 500016, India; Dr. NTR University of Health Sciences, Vijayawada 500008, Andhra Pradesh, India.
authors.forename: Uzma
authors.initials: U
authors.lastname: Shaheen
authors.affiliation: Dr. Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation, Gannavaram, Andhra Pradesh, India.
authors.forename: U
authors.initials: U
authors.lastname: Satyanarayana
authors.affiliation: Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, India.
authors.forename: T Surya
authors.initials: TS
authors.lastname: Prabha
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad 500016, India.
authors.forename: A
authors.initials: A
authors.lastname: Jyothy
authors.affiliation: Centre for Human Genetics, Central University of Punjab, Bathinda 151001, Punjab, India. Electronic address: anjanadurani@yahoo.co.in.
authors.forename: Anjana
authors.initials: A
authors.lastname: Munshi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004829:Epilepsy, Generalized / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics*; D016704:Synapsins / Q000235:genetics*; D055815:Young Adult
chemical_list: C546171:GABRA6 protein, human; D011963:Receptors, GABA-A; D016704:Synapsins
keywords: Epileptogenesis; Gamma-amino butyric acid (GABA); Gene–gene interaction; Idiopathic generalized epilepsies; Neurotransmitter; Synapsin II