SCN2A基因多态性与儿童癫痫抗癫痫药物疗效的相关性研究  

Correlation between SCN2A gene polymorphism and the efficacy of antiepileptic drugs in children with epilepsy

作　　者：王春霞[1] 段文浩 王左华 聂文莎 郑宇霞[1] 王惠萍[1] WANG Chun-xia;DUAN Wen-hao;WANG Zuo-hua(Kunming Children's Hospital(Children's Hospital Affiliated to Kunming Medical University),Kunming Yunnan 650228,China)

机构地区：[1]昆明市儿童医院(昆明医科大学附属儿童医院),云南昆明650228

出　　处：《临床和实验医学杂志》2024年第24期2651-2654,共4页Journal of Clinical and Experimental Medicine

基　　金：云南省科技厅基础研究计划项目(编号:202101AY070001-218);云南省“兴滇英才支持计划”医疗卫生人才专项支持项目(编号:XDYC-YLWS-2023-0005);昆明市卫生健康委员会卫生科研课题项目(编号:2020-06-04-114);昆明市医学中心建设项目【编号:2022-SW(技术)-19】。

摘　　要：目的探讨钠通道电压门控2A(SCN2A)基因多态性与儿童癫痫抗癫痫药物(AED)疗效的相关性。方法选取2019年9月至2023年3月昆明市儿童医院收治的癫痫患儿95例,按服用AED后12个月内癫痫发作情况将患儿分为两组,其中未发生癫痫者作为有效组(n=63),癫痫发作频率不变甚至增加者作为无效组(n=32)。使用qRT-PCR对患儿SCN2A位点rs17183814基因型进行检测。比较各组SCN2A基因型差异和临床资料差异,应用Spearman相关分析法对SCN2A基因型与药物疗效之间的相关性进行分析,并用Logistic回归模型确定AED耐药的危险因素。结果两组年龄、性别、体重和首次发作年龄比较,差异均无统计学意义(P>0.05);两组首次发作类型、脑电图检查结果、发作频率和AED种类比较,差异均有统计学意义(P<0.05);无效组发作类型为肌阵挛的比例、发作频率、脑电图检查结果异常的比例、左乙拉西坦的比例均显著高于有效组,差异均有统计学意义(P<0.05)。相比AED反应组,AED耐药组SCN2A基因位点rs17183814 AA基因型的比例更高,A基因分布频率更高,差异有统计学意义(P<0.05)。有效组患儿SCN2A的AG基因型、GG型与左乙拉西坦呈正相关(P<0.05);无效组患儿AA型与丙戊酸呈正相关(P<0.05)。Logistic回归分析表明,发作频率(OR=8.199,95%CI:1.372~48.985)和SCN2A基因多态性(OR=8.199,95%CI:1.372~48.985)是癫痫患儿AED治疗疗效的独立影响因素(P<0.05),其中AA基因型相比GG型+AG型治疗无效的风险显著更高。结论SCN2A基因多态性与与儿童癫痫AED治疗疗效相关,特别是AA基因型为治疗无效的风险因素,此外发作频率较高者也易出现无效。Objective To investigate the correlation between sodium channel voltage-gated 2A(SCN2A)gene polymorphism and the efficacy of antiepileptic drugs(AED)in children with epilepsy.Methods A total of 95 children with epilepsy admitted to Kunming Children's Hospital from September 2019 to March 2023 were retrospectively selected.The children were divided into two groups according to the seizures within 12 months after taking AED,and those without epilepsy were taken as the effective group(n=63).Patients with unchanged or even increased seizure frequency were considered as ineffective group(n=32).The genotype of rs17183814 in SCN2A locus was detected by qRT-PCR.The differences of SCN2A genotype and clinical data were compared among the groups.The correlation between SCN2A genotype and drug efficacy was analyzed using Spearman correlation analysis,and the risk factors of AED resistance was determined using Logistic regression model.Results There were no statistically significant differences in age,sex,weight and age of first attack between the two groups(P>0.05).There were statistically significant differences in the first seizure type,EEG examination results,seizure frequency and AED types between the two groups(P<0.05).The proportion of myoclonus,seizure frequency,abnormal EEG results and levetiracetam in the ineffective group were significantly higher than those in the effective group,and the differences were statistically significant(P<0.05).Compared with the AED response group,the proportion of AA genotype of SCN2A gene locus rs17183814 in the AED resistance group was higher,and the frequency of A gene distribution was higher,the difference was statistically significant(P<0.05).The AG genotype and GG genotype of SCN2A in the effective group were positively correlated with levetiracetam(P<0.05).In the ineffective group,AA type was positively correlated with valproic acid(P<0.05).Logistic regression analysis showed that seizure frequency(OR=8.199,95%CI:1.372-48.985)and SCN2A gene polymorphism(OR=8.199,95%CI:1.372-48.98

关 键 词：癫痫 儿童 抗癫痫药物疗效 钠通道电压门控2A 基因多态性 

分 类 号：R74[医药卫生—神经病学与精神病学]