普洱地区少数民族不同表型癫痫儿童基因多态性与抗癫痫药应答之间的关系研究

Study on the relationship between gene polymorphism and antiepileptic drug response in minority children with different phenotypes of epilepsy in Pu'er region

目的分析普洱地区少数民族不同表型癫痫儿童基因多态性与抗癫痫药应答之间的关系。方法选取2021年1月至2022年1月普洱市人民医院儿科门诊就诊并确诊为癫痫的129例患儿,均行二代测序,其中82例明确致病基因[电压门控钠离子通道(SCN)1A、SCN2A、电压门控氯离子通道2(CLCN2)、T型钙离子通道α1H亚基(CACNA1H)],依据基因测序结果,对82例明确致病基因患儿进行研究,给予抗癫痫药物治疗,根据治疗效果分为有效组(n=62)、无效组(n=20),收集两组患儿临床资料、SCN1A、CLCN2、SCN2A、CACNA1H基因型和等位基因频率,用Logistic分析抗癫痫药应答情况的影响因素。结果两组发作频率、脑电图表现、SCN1A rs3812718、SCN2A rs17183814、CACNA1H rs9922076基因型分布及等位基因频率比较,差异有统计学意义(P<0.05),CLCN2 rs6770808基因型分布及等位基因频率比较,差异无统计学意义(P>0.05);有效组SCN1A rs3812718基因型GA及等位基因A、SCN2A rs17183814基因型GG及等位基因G、CACNA1H rs9922076基因型CC及等位基因C高于无效组(P<0.05);Logistic显示,SCN1A rs3812718基因型GA、SCN2A rs17183814基因型GG、CACNA1H rs9922076基因型CC是抗癫痫药治疗癫痫患儿的影响因素(P<0.05)。结论普洱地区少数民族癫痫患儿SCN1A rs3812718、SCN2A rs17183814、CACNA1H rs9922076基因多态性与抗癫痫药物疗效有关,上述基因位点突变对临床治疗癫痫患儿具有一定指导意义。

Objective To analyze the relationship between gene polymorphism and anti epileptic drug response in children with different phenotypes of epilepsy among ethnic minorities in Pu'er region.Methods From January 2021 to January 2022,129 children who were diagnosed as epilepsy in the pediatric clinic of Pu'er People's Hospital were selected for second-generation sequencing,82 of whom identified the pathogenic genes[voltage-gated Sodium channel(SCN)1A,SCN2A,voltage-gated chloride Ion channel 2(CLCN2),and T-type calcium Ion channelα1H subunit(CACNA1H)],according to the results of gene sequencing,82 children with confirmed pathogenic genes were studied and given antiepileptic drugs.According to the treatment effect,they were divided into effective group(n=62)and ineffective group(n=20).The clinical data,SCN1A,CLCN2,SCN2A,CACNA1H genotypes and Allele frequency of the two groups were collected,and the influencing factors of antiepileptic drug response were analyzed with Logistic.Results The differences in seizure frequency,EEG performance,SCN1A rs3812718,SCN2A rs17183814,CACNA1H rs9922076 genotype distribution and allele frequency between the two groups were statistically significant(P<0.05),while the differences in CLCN2 rs6770808 genotype distribution and allele frequency were not statistically significant(P>0.05).The effective group had higher genotype GA and allele A of SCN1A rs3812718,genotype GG and allele G of SCN2A rs17183814,and genotype CC and allele C of CACNA1H rs9922076than the ineffective group(P<0.05).Logistic showed that SCN1A rs3812718 genotype GA,SCN2A rs17183814 genotype GG,and CACNA1H rs9922076 genotype CC were influential factors in children with epilepsy treated with antiepileptic drugs(P<0.05).Conclusion The gene polymorphisms of SCN1A rs3812718,SCN2A rs17183814,and CACNA1H rs9922076 are related to the efficacy of antiepileptic drugs in minority children with epilepsy in Pu'er area.The above gene locus mutation has certain guiding significance for clinical treatment of children with epilepsy.