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
Department of Neurosurgery, Xiangya Hospital, Central South University, 410008, Changsha, China.
Department of Cardiology, the First Affiliated Hospital of Henan Collede of TCM, 450008, Zhengzhou, China.
PLoS One. 2015 Apr 13;10(4):e0124896. doi: 10.1371/journal.pone.0124896. eCollection 2015.
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.
由于遗传泛化性癫痫（GGEs）复杂的遗传模式和遗传异质性，探索其遗传机制具有挑战性。KCNJ10基因编码Kir4.1通道，在调节可兴奋细胞的静息膜电位中起主要作用。该基因发生突变时可能导致GGEs。本研究旨在探讨中国人群中KCNJ10常见变异与GGEs易感性及耐药性之间的可能关联。采用等位基因特异性基质辅助激光解吸电离飞行时间质谱法，对284名健康对照者和483名中国GGEs患者（包括279名抗癫痫药物反应性患者和204名耐药患者）的KCNJ10基因的8个单核苷酸多态性（SNP）进行评估。我们发现，GGEs组中rs6690889的TC + TT基因型频率低于健康对照组（6.7%对9.5%，p = 0.01，OR = 0.50[0.29 - 0.86]）。儿童失神癫痫（CAE）组中rs1053074的G等位基因频率低于健康对照组（28.4%对36.2%，p = 0.01，OR = 0.70[0.53 - 0.93]）。CAE组中rs12729701的G等位基因频率以及AG + GG基因型频率均低于健康对照组（分别为21.2%对28.4%，p = 0.01，OR = 0.74[0.59 - 0.94]；36.3%对48.1%，p = 0.01，OR = 0.83[0.72 - 0.96]）。GGEs药物反应性患者中rs12402969的C等位基因频率以及CC + CT基因型频率高于耐药患者（分别为9.3%对5.6%，OR = 1.73[1.06 - 2.85]，p = 0.026；36.3%对48.1%，p = 0.01，OR = 0.83[0.72 - 0.96]）。本研究确定了KCNJ10基因中可能与癫痫易感性和抗癫痫药物耐药性相关的潜在SNP。
