title: Synergistic association of STX1A and VAMP2 with cryptogenic epilepsy in North Indian population.
abstract: "Common epilepsies", merely explored for genetics are the most frequent, nonfamilial, sporadic cases in hospitals. Because of their much debated molecular pathology, there is a need to focus on other neuronal pathways including the existing ion channels.
  
  
  
  For this study, a total of 214 epilepsy cases of North Indian ethnicity comprising 59.81% generalized, 40.19% focal seizures, and based on epilepsy types, 17.29% idiopathic, 37.38% cryptogenic, and 45.33% symptomatic were enrolled. Additionally, 170 unrelated healthy individuals were also enrolled. Here, we hypothesize the involvement of epilepsy pathophysiology genes, that is, synaptic vesicle cycle, SVC genes (presynapse), ion channels and their functionally related genes (postsynapse). An interactive analysis was initially performed in SVC genes using multifactor dimensionality reduction (MDR). Further, in order to understand the influence of ion channels and their functionally related genes, their interaction analysis with SVC genes was also performed.
  
  
  
  A significant interactive two-locus model of STX1A_rs4363087|VAMP2_rs2278637 (presynaptic genes) was observed among SVC variants in all epilepsy cases (P 1000-value = 0.054; CVC = 9/10; OR = 2.86, 95%CI = 1.88-4.35). Further, subgroup analysis revealed stronger interaction for the same model in cryptogenic epilepsy patients only (P 1000-value = 0.012; CVC = 10/10; OR = 4.59, 95%CI = 2.57-8.22). However, interactive analysis of presynaptic and postsynaptic genes did not show any significant association.
  
  
  
  Significant synergistic interaction of SVC genes revealed the possible functional relatedness of presynapse with pathophysiology of cryptogenic epilepsy. Further, to establish the clinical utility of the results, replication in a large and similar phenotypic group of patients is warranted.
authors.affiliation: Council of Scientific and Industrial Research (CSIR) Institute of Genomics and Integrative Biology (IGIB) Mall Road Delhi 110 007 India.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Baghel
authors.affiliation: Council of Scientific and Industrial Research (CSIR) Institute of Genomics and Integrative Biology (IGIB) Mall Road Delhi 110 007 India; Division of Pneumonology-Immunology Department of Paediatrics Charité University Medical Centre Berlin Germany.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Grover
authors.affiliation: Council of Scientific and Industrial Research (CSIR) Institute of Genomics and Integrative Biology (IGIB) Mall Road Delhi 110 007 India.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Kaur
authors.affiliation: Council of Scientific and Industrial Research (CSIR) Institute of Genomics and Integrative Biology (IGIB) Mall Road Delhi 110 007 India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Jajodia
authors.affiliation: Council of Scientific and Industrial Research (CSIR) Institute of Genomics and Integrative Biology (IGIB) Mall Road Delhi 110 007 India.
authors.forename: Shama
authors.initials: S
authors.lastname: Parween
authors.affiliation: Council of Scientific and Industrial Research (CSIR) Institute of Genomics and Integrative Biology (IGIB) Mall Road Delhi 110 007 India.
authors.forename: Juhi
authors.initials: J
authors.lastname: Sinha
authors.affiliation: Council of Scientific and Industrial Research (CSIR) Institute of Genomics and Integrative Biology (IGIB) Mall Road Delhi 110 007 India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Neurology Department Neuroscience Centre All India Institute of Medical Sciences (AIIMS) New Delhi India.
authors.forename: Achal Kumar
authors.initials: AK
authors.lastname: Srivastava
authors.affiliation: Institute of Human Behavior & Allied Sciences (IHBAS) Dilshad Garden Delhi 110 095 India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Bala
authors.affiliation: AceProbe Technologies (India) Pvt. Ltd. New Delhi India.
authors.forename: Puneet
authors.initials: P
authors.lastname: Chandna
authors.affiliation: Institute of Human Behavior & Allied Sciences (IHBAS) Dilshad Garden Delhi 110 095 India.
authors.forename: Suman
authors.initials: S
authors.lastname: Kushwaha
authors.affiliation: Institute of Human Behavior & Allied Sciences (IHBAS) Dilshad Garden Delhi 110 095 India.
authors.forename: Rachna
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Council of Scientific and Industrial Research (CSIR) Institute of Genomics and Integrative Biology (IGIB) Mall Road Delhi 110 007 India.
authors.forename: Ritushree
authors.initials: R
authors.lastname: Kukreti
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000453:epidemiology / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D050827:Syntaxin 1 / Q000235:genetics*; D050988:Vesicle-Associated Membrane Protein 2 / Q000235:genetics*; D055815:Young Adult
chemical_list: C494212:STX1A protein, human; D050827:Syntaxin 1; C494807:VAMP2 protein, human; D050988:Vesicle-Associated Membrane Protein 2
keywords: Common epilepsy; STX1A; Synaptic vesicle cycle; VAMP2; epistasis; interaction; ion channels