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Common Variants of KCNJ10 Are Associated with Susceptibility and Anti-Epileptic Drug Resistance in Chinese Genetic Generalized Epilepsies
To explore genetic mechanism of genetic generalized epilepsies (GGEs) is challenging because of their complex heritance pattern and genetic heterogeneity. KCNJ10 gene encodes Kir4.1 channels and plays a major role in modulating resting membrane potentials in excitable cells. It may cause GGEs if mut...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395153/ https://www.ncbi.nlm.nih.gov/pubmed/25874548 http://dx.doi.org/10.1371/journal.pone.0124896 |
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author | Guo, Yong Yan, Kui Po Qu, Qiang Qu, Jian Chen, Zi Gui Song, Tao Luo, Xiang-Ying Sun, Zhong-Yi Bi, Chang-Long Liu, Jin-Fang |
author_facet | Guo, Yong Yan, Kui Po Qu, Qiang Qu, Jian Chen, Zi Gui Song, Tao Luo, Xiang-Ying Sun, Zhong-Yi Bi, Chang-Long Liu, Jin-Fang |
author_sort | Guo, Yong |
collection | PubMed |
description | To explore genetic mechanism of genetic generalized epilepsies (GGEs) is challenging because of their complex heritance pattern and genetic heterogeneity. KCNJ10 gene encodes Kir4.1 channels and plays a major role in modulating resting membrane potentials in excitable cells. It may cause GGEs if mutated. The purpose of this study was to investigate the possible association between KCNJ10 common variants and the susceptibility and drug resistance of GGEs in Chinese population. The allele-specific MALDI–TOF mass spectrometry method was used to assess 8 single nucleotide polymorphisms (SNPs) of KCNJ10 in 284 healthy controls and 483 Chinese GGEs patients including 279 anti-epileptic drug responsive patients and 204 drug resistant patients. We found the rs6690889 TC+TT genotypes were lower frequency in the GGEs group than that in the healthy controls (6.7% vs 9.5%, p = 0.01, OR = 0.50[0.29–0.86]). The frequency of rs1053074 G allele was lower in the childhood absence epilepsy (CAE) group than that in the healthy controls (28.4% vs 36.2%, p = 0.01, OR = 0.70[0.53–0.93]). The frequency of rs12729701 G allele and AG+GG genotypes was lower in the CAE group than that in the healthy controls (21.2% vs 28.4%, p = 0.01, OR = 0.74[0.59–0.94] and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72–0.96], respectively). The frequency of rs12402969 C allele and the CC+CT genotypes were higher in the GGEs drug responsive patients than that in the drug resistant patients (9.3% vs 5.6%, OR = 1.73[1.06–2.85], p = 0.026 and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72–0.96], respectively). This study identifies potential SNPs of KCNJ10 gene that may contribute to seizure susceptibility and anti-epileptic drug resistance. |
format | Online Article Text |
id | pubmed-4395153 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43951532015-04-21 Common Variants of KCNJ10 Are Associated with Susceptibility and Anti-Epileptic Drug Resistance in Chinese Genetic Generalized Epilepsies Guo, Yong Yan, Kui Po Qu, Qiang Qu, Jian Chen, Zi Gui Song, Tao Luo, Xiang-Ying Sun, Zhong-Yi Bi, Chang-Long Liu, Jin-Fang PLoS One Research Article To explore genetic mechanism of genetic generalized epilepsies (GGEs) is challenging because of their complex heritance pattern and genetic heterogeneity. KCNJ10 gene encodes Kir4.1 channels and plays a major role in modulating resting membrane potentials in excitable cells. It may cause GGEs if mutated. The purpose of this study was to investigate the possible association between KCNJ10 common variants and the susceptibility and drug resistance of GGEs in Chinese population. The allele-specific MALDI–TOF mass spectrometry method was used to assess 8 single nucleotide polymorphisms (SNPs) of KCNJ10 in 284 healthy controls and 483 Chinese GGEs patients including 279 anti-epileptic drug responsive patients and 204 drug resistant patients. We found the rs6690889 TC+TT genotypes were lower frequency in the GGEs group than that in the healthy controls (6.7% vs 9.5%, p = 0.01, OR = 0.50[0.29–0.86]). The frequency of rs1053074 G allele was lower in the childhood absence epilepsy (CAE) group than that in the healthy controls (28.4% vs 36.2%, p = 0.01, OR = 0.70[0.53–0.93]). The frequency of rs12729701 G allele and AG+GG genotypes was lower in the CAE group than that in the healthy controls (21.2% vs 28.4%, p = 0.01, OR = 0.74[0.59–0.94] and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72–0.96], respectively). The frequency of rs12402969 C allele and the CC+CT genotypes were higher in the GGEs drug responsive patients than that in the drug resistant patients (9.3% vs 5.6%, OR = 1.73[1.06–2.85], p = 0.026 and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72–0.96], respectively). This study identifies potential SNPs of KCNJ10 gene that may contribute to seizure susceptibility and anti-epileptic drug resistance. Public Library of Science 2015-04-13 /pmc/articles/PMC4395153/ /pubmed/25874548 http://dx.doi.org/10.1371/journal.pone.0124896 Text en © 2015 Guo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Guo, Yong Yan, Kui Po Qu, Qiang Qu, Jian Chen, Zi Gui Song, Tao Luo, Xiang-Ying Sun, Zhong-Yi Bi, Chang-Long Liu, Jin-Fang Common Variants of KCNJ10 Are Associated with Susceptibility and Anti-Epileptic Drug Resistance in Chinese Genetic Generalized Epilepsies |
title | Common Variants of KCNJ10 Are Associated with Susceptibility and Anti-Epileptic Drug Resistance in Chinese Genetic Generalized Epilepsies |
title_full | Common Variants of KCNJ10 Are Associated with Susceptibility and Anti-Epileptic Drug Resistance in Chinese Genetic Generalized Epilepsies |
title_fullStr | Common Variants of KCNJ10 Are Associated with Susceptibility and Anti-Epileptic Drug Resistance in Chinese Genetic Generalized Epilepsies |
title_full_unstemmed | Common Variants of KCNJ10 Are Associated with Susceptibility and Anti-Epileptic Drug Resistance in Chinese Genetic Generalized Epilepsies |
title_short | Common Variants of KCNJ10 Are Associated with Susceptibility and Anti-Epileptic Drug Resistance in Chinese Genetic Generalized Epilepsies |
title_sort | common variants of kcnj10 are associated with susceptibility and anti-epileptic drug resistance in chinese genetic generalized epilepsies |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395153/ https://www.ncbi.nlm.nih.gov/pubmed/25874548 http://dx.doi.org/10.1371/journal.pone.0124896 |
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