中国临床药理学杂志2025，Vol.41Issue(17)：2412-2417,6.DOI:10.13699/j.cnki.1001-6821.2025.17.003
难治性癫痫患者癫痫耐药与全外显子组基因多态性相关性的临床研究
Clinical trial on the association between epilepsy drug resistance and whole exome genetic polymorphisms in refractory epilepsy patients
摘要
Abstract
Objective To investigate the association between drug resistant epilepsy(DRE)and single nucleotide polymorphisms(SNPs)in whole-exome sequencing(WES).Methods Patients with epilepsy,who visited in our hospital,were enrolled in this study and divided into a drug-resistant group and a monotherapy-effective group based on treatment outcomes.Baseline demographic characteristics,medical history and laboratory test results were collected.Seizure outcomes were observed after more than 12 months under adequate treatment.WES was performed on 12 extreme cases(6 patients with resistant to three antiepileptic drugs vs.6 patients effectively treated with monotherapy and undergoing dose reduction)to identify candidate SNPs.These candidate SNPs were then validated in the larger cohort to explore the association with DRE.Results A tota of 560 patients were enrolled,153 were DRE group and 407 were monotherapy-effective group.The median age in the monotherapy-effective group and the drug-resistant group was 19 years old and 25 years old,respectively;the median weight were 50 kg and 55 kg,respectively.All these differences between the two groups were statistically significant(all P＜0.05);the proportion of structural etiology was 55.56％in the drug-resistant group and 45.46％in the monotherapy-effective group;the proportion of infectious etiology were 3.92％and 2.21％;the proportion of immune etiology were 3.27％and 1.23％;the proportion of metabolic and genetic etiology were 5.88％and 11.30％;the proportion of dual etiologies were 1.96％and 1.23％;the proportion of patients with impaired consciousness were 56.21％and 39.07％;the proportion of second-generation antiseizure medication as initial medication regimen were 50.98％and 65.46％;the proportion of malformation of cortical development were 10.46％and 2.95％;the proportion of hippocampal sclerosis were 15.03％and 9.58％;the proportion of hypoxic-ischemic encephalopathy were 3.92％and 1.47％;the proportion of vascular malformation were 4.58％and 3.93％;the proportion of traumatic brain injury were 1.31％and 3.44％;the proportion with brain tumor were 3.92％and 2.21％;the proportion with dual pathologies were 1.96％and 0.98％;the proportion of abnormal nonepileptogenic were 23.53％and 29.48％.Baseline information showed statistically significant differences in age,weight,etiology,presence of impaired awareness,initial medication regimen and neuroimaging results(P＜0.05,P＜0.001).102 candidate SNPs were selected for genotyping and association analysis in larger cohort including 560 patients.5 SNPs were identified to be significantly associated with DRE.Multivariate logistic regression incorporating both clinical and genetic factors revealed that hippocampal sclerosis,malformation of cortical development,hypoxic-ischemic,presence of impaired awareness,as well as the SCN2A rs17183814 GG and SPATA31 rs1919128 GA genotypes were risk factors for drug resistance(SCN2A rs17183814 GG:P=0.027;SPATA31 rs1919128 GA:P=0.014).Conclusion SCN2A rs17183814 and SPATA31 rs1919128 were found to be associated with drug resistance.Carriers of the GG genotypes of SCN2A rs17183814 and GA genotype of SPATA31 rs1919128 are more likely to develop DRE.关键词
癫痫/耐药/单核苷酸多态性/全外显子组测序/临床研究Key words
epilepsy/drug resistance/single-nucleotide polymorphisms/whole-exome sequencing/clinical study分类
医药卫生引用本文复制引用
刘松泽,李蕊彤,陈子怡,唐思媛,张晓旭,任瑞娜,王雪丁,黄民..难治性癫痫患者癫痫耐药与全外显子组基因多态性相关性的临床研究[J].中国临床药理学杂志,2025,41(17):2412-2417,6.基金项目
国家自然科学基金资助项目(81730103 （）
81973398) （）
广东省重点实验室基金资助项目(2017B030314030) （2017B030314030）
