GABAARG2基因单核苷酸多态性与儿童癫痫易感性的关系
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摘要
目的对我国北方地区汉族儿童GABAARG2基因C588T单核苷酸多态性与癫痫易感性的关系进行研究。方法选取2013年3月—2018年6月于延边大学附属医院儿科门诊和/或住院治疗的189例癫痫患儿作为研究对象。根据癫痫发作类型分为部分性发作组和全面性发作组,同时选择113例非癫痫儿童作为对照组。收集研究对象一般临床资料,提取外周血基因组DNA,采用PCR扩增后基因测序鉴定GABAARG2基因C588T多态性,测定该位点基因型频率和等位基因频率,并进行统计学分析。结果 3组患儿平均病程、24 h脑电图中度以上异常比较,差异有统计学意义(P<0.05)。3组患者CC、CT和TT基因型比较,差异有统计学意义(P <0.05);3组患者等位基因C、T频率比较,差异有统计学意义(P <0.05)。相比与CC基因型,CT基因型引发癫痫的风险是其2.127倍,TT基因型则为3.926倍;相比C等位基因,T等位基因引发癫痫的风险是其2.191倍。结论 GABAARG2基因C588T单核苷酸多态性与儿童癫痫的易感性有关。
Objective To investigate the association between the C588 T single nucleotide polymorphism of GABAARG2 gene and epilepsy susceptibility in Han children in northern China. Methods A total of 189 children with epilepsy who came to our pediatric clinic and/or hospitalization from March 2013 to June 2018 were selected as subjects. According to the types of epileptic seizures, subjects were divided into partial seizure group(n = 107)and generalized seizure group(n = 82). At the same time, 113 non-epileptic children were selected as control group.General clinical data of all patients were collected. Genomic DNA was extracted from peripheral blood of all subjects, and the C588 T polymorphism of GABAARG2 gene was identified by PCR amplification. Genotype and allele frequencies of this locus were determined and analyzed statistically. Results There were significant differences in the average course of disease and abnormal EEG at 24 hours in three groups(P < 0.05). There were significant differences in genotypes of CC, CT and TT and allele C and T frequencies in three groups(P < 0.05). Compared with CC genotype, the risk of epilepsy induced by CT genotype was 2.127 times(95% CI: 1.23, 3.615, P < 0.05) and TT genotype was 3.926 times(95% CI: 2.019, 7.51, P < 0.05). Compared with the C allele, the risk of epilepsy induced by T allele was 2.191 times(95% CI:1.554, 3.094, P < 0.05). Conclusions The single nucleotide polymorphism of GABAARG2 gene C588 T is associated with susceptibility to epilepsy in children.
Objective To investigate the association between the C588 T single nucleotide polymorphism of GABAARG2 gene and epilepsy susceptibility in Han children in northern China. Methods A total of 189 children with epilepsy who came to our pediatric clinic and/or hospitalization from March 2013 to June 2018 were selected as subjects. According to the types of epileptic seizures, subjects were divided into partial seizure group(n = 107)and generalized seizure group(n = 82). At the same time, 113 non-epileptic children were selected as control group.General clinical data of all patients were collected. Genomic DNA was extracted from peripheral blood of all subjects, and the C588 T polymorphism of GABAARG2 gene was identified by PCR amplification. Genotype and allele frequencies of this locus were determined and analyzed statistically. Results There were significant differences in the average course of disease and abnormal EEG at 24 hours in three groups(P < 0.05). There were significant differences in genotypes of CC, CT and TT and allele C and T frequencies in three groups(P < 0.05). Compared with CC genotype, the risk of epilepsy induced by CT genotype was 2.127 times(95% CI: 1.23, 3.615, P < 0.05) and TT genotype was 3.926 times(95% CI: 2.019, 7.51, P < 0.05). Compared with the C allele, the risk of epilepsy induced by T allele was 2.191 times(95% CI:1.554, 3.094, P < 0.05). Conclusions The single nucleotide polymorphism of GABAARG2 gene C588 T is associated with susceptibility to epilepsy in children.
引文
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[15]梁维,许志恩,方洪明.GABAARG2基因C588T多态性与癫痫的相关性研究[J].中风与神经疾病,2016,33(2):139-142.
[16]王加朋,梁彩艳.KCNJ10基因rs1890532单核苷酸多态性与儿童癫痫易感性的相关性研究[J].中国神经精神疾病杂志,2017,43(6):336-340.
[2]HAERIAN B S,BAUM L.GABRG2 rs211037 polymorphism and epilepsy:a systematic review and meta-analysis[J].Seizure,2013,22(1):53-58.
[3]张虎,杜欣娜,徐敏,等.GABAA受体基因多态性与癫痫易感性的关系[J].中国老年学,2015(19):5439-5441.
[4]SALAM S M,RAHMAN H M,KARAM R A.GABRG2gene polymorphisms in Egyptian children with simple febrile seizures[J].Indian Journal of Pediatrics,2012,79(11):1514-1516.
[5]LISTED N.Proposal for revised clinical and electroencephalographic classification of epileptic seizures from the commission on classification and terminology of the international league against epilepsy[J].Epilepsia,1981,22(4):489-501.
[6]韦秀娟.小儿癫痫的临床治疗与护理干预措施探讨[J].河北医学,2014(10):1742-1744.
[7]陶哲,伊文霞,韩颖,等.儿童癫痫发作的远期预后及相关因素[J].北京大学学报(医学版),2014,46(2):315-318.
[8]李国强,王剑,傅启华.癫痫的遗传学研究进展[J].国际检验医学杂志,2015(23):3459-3462.
[9]徐敏,王菊莉,张虎.GABAA受体亚基变异与癫痫易感性关系的研究进展[J].中国伤残医学,2014(20):220-222.
[10]戚月凤,汤继宏,李岩,等.GABAA受体γ2亚单位在海人酸颞叶癫痫大鼠海马内的表达[J].神经损伤与功能重建,2015(2):110-112.
[11]伍国锋,史静,洪震,等.耐药性杏仁核点燃癫痫模型海马组织中γ-氨基丁酸受体表达变化[J].中华神经科杂志,2013,46(10):702-705.
[12]TERUNUMA M,XU J,VITHLANI M,et al.Deficits in phosphorylation of GABA(A)receptors by intimately associated protein kinase C activity underlie compromised synaptic inhibition during status epilepticus[J].Journal of Neuroscience,2008,28(2):376-384.
[13]杜芳宇.吡格列酮对哮喘小鼠肺组织GABAARα及MUC5AC表达的影响[D].郑州:郑州大学,2014(1):33-36.
[14]刘昕,胡崇宇,高小平,等.癫痫持续状态NKCC1,GABAARα1蛋白在大鼠海马的表达及脑源性神经营养因子对其的影响[J].中国现代医学杂志,2015,25(18):1-7.
[15]梁维,许志恩,方洪明.GABAARG2基因C588T多态性与癫痫的相关性研究[J].中风与神经疾病,2016,33(2):139-142.
[16]王加朋,梁彩艳.KCNJ10基因rs1890532单核苷酸多态性与儿童癫痫易感性的相关性研究[J].中国神经精神疾病杂志,2017,43(6):336-340.