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Synergistic association of STX1A and VAMP2 with cryptogenic epilepsy in North Indian population

INTRODUCTION: “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. METHODS: For this study, a tota...

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Autores principales: Baghel, Ruchi, Grover, Sandeep, Kaur, Harpreet, Jajodia, Ajay, Parween, Shama, Sinha, Juhi, Srivastava, Ankit, Srivastava, Achal Kumar, Bala, Kiran, Chandna, Puneet, Kushwaha, Suman, Agarwal, Rachna, Kukreti, Ritushree
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951625/
https://www.ncbi.nlm.nih.gov/pubmed/27458546
http://dx.doi.org/10.1002/brb3.490
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author Baghel, Ruchi
Grover, Sandeep
Kaur, Harpreet
Jajodia, Ajay
Parween, Shama
Sinha, Juhi
Srivastava, Ankit
Srivastava, Achal Kumar
Bala, Kiran
Chandna, Puneet
Kushwaha, Suman
Agarwal, Rachna
Kukreti, Ritushree
author_facet Baghel, Ruchi
Grover, Sandeep
Kaur, Harpreet
Jajodia, Ajay
Parween, Shama
Sinha, Juhi
Srivastava, Ankit
Srivastava, Achal Kumar
Bala, Kiran
Chandna, Puneet
Kushwaha, Suman
Agarwal, Rachna
Kukreti, Ritushree
author_sort Baghel, Ruchi
collection PubMed
description INTRODUCTION: “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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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spelling pubmed-49516252016-07-25 Synergistic association of STX1A and VAMP2 with cryptogenic epilepsy in North Indian population Baghel, Ruchi Grover, Sandeep Kaur, Harpreet Jajodia, Ajay Parween, Shama Sinha, Juhi Srivastava, Ankit Srivastava, Achal Kumar Bala, Kiran Chandna, Puneet Kushwaha, Suman Agarwal, Rachna Kukreti, Ritushree Brain Behav Original Research INTRODUCTION: “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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. John Wiley and Sons Inc. 2016-06-14 /pmc/articles/PMC4951625/ /pubmed/27458546 http://dx.doi.org/10.1002/brb3.490 Text en © 2016 The Authors. Brain and Behavior published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Baghel, Ruchi
Grover, Sandeep
Kaur, Harpreet
Jajodia, Ajay
Parween, Shama
Sinha, Juhi
Srivastava, Ankit
Srivastava, Achal Kumar
Bala, Kiran
Chandna, Puneet
Kushwaha, Suman
Agarwal, Rachna
Kukreti, Ritushree
Synergistic association of STX1A and VAMP2 with cryptogenic epilepsy in North Indian population
title Synergistic association of STX1A and VAMP2 with cryptogenic epilepsy in North Indian population
title_full Synergistic association of STX1A and VAMP2 with cryptogenic epilepsy in North Indian population
title_fullStr Synergistic association of STX1A and VAMP2 with cryptogenic epilepsy in North Indian population
title_full_unstemmed Synergistic association of STX1A and VAMP2 with cryptogenic epilepsy in North Indian population
title_short Synergistic association of STX1A and VAMP2 with cryptogenic epilepsy in North Indian population
title_sort synergistic association of stx1a and vamp2 with cryptogenic epilepsy in north indian population
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951625/
https://www.ncbi.nlm.nih.gov/pubmed/27458546
http://dx.doi.org/10.1002/brb3.490
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