microRNA基因单核苷酸多态性与丙戊酸抗癫痫疗效的相关性  

Association of microRNA gene polymorphisms and the efficacy of valproic acid in epileptic patients

作　　者：任瑞娜 李蕊彤 唐思媛 周列民[2] 陈子怡[2] 倪冠中[2] 王雪丁[1] 黄民[1] REN Rui-na;LI Rui-tong;TANG Si-yuan;ZHOU Lie-min;CHEN Zi-yi;NI Guan-zhong;WANG Xue-ding;HUANG Min(Institute of Clinical Pharmacology,School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510080,Guangdong Province,China;Department of Neurology,Epilepsy Center,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,Guangdong Province,China)

机构地区：[1]中山大学药学院临床药理研究所,广东广州510080 [2]中山大学附属第一医院神经内科,广东广州510080

出　　处：《中国临床药理学杂志》2022年第8期763-767,共5页The Chinese Journal of Clinical Pharmacology

基　　金：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)。

摘　　要：目的考察microRNA(miRNA)基因单核苷酸多态性与癫痫患者中丙戊酸(VPA)疗效的相关性。方法试验纳入155例单用VPA的癫痫患者,采集外周静脉血4 mL。所有患者均每日口服VPA 250~1500 mg进行治疗,并随访记录12个月以上的癫痫发作情况。将完成试验的138例癫痫患者根据癫痫发作情况分为有效控制组99例和未有效控制组39例。采用Agena MassARRAY平台对14个候选miRNA基因的单核苷酸多态性位点进行检测,并利用卡方检验分析不同位点的基因多态性与VPA抗癫痫疗效的关系。结果MIR5090 rs3823658 GA基因型在有效控制组中的分布频率明显高于未有效控制组(30.61%vs.13.51%,P<0.05),且二元logistic回归分析表明GA基因型是VPA疗效的保护因素(OR=3.187,P<0.05),可解释6.2%的个体差异。MIR8063 rs7183051显性模型GG/GA+AA在2组间的分布具有统计学差异(P<0.05),GA+AA基因型在有效控制组的分布频率明显高于未有效控制组(31.96%vs.15.38%,P<0.05)。除此之外,本研究未发现其余单核苷酸多态性与VPA疗效的相关性。结论MIR5090 rs3823658 GA基因型可能是癫痫患者中VPA疗效的保护因素。Objective To investigate the correlation between microRNA(miRNA)gene single nucleotide polymorphism(SNP)and the efficacy of valproic acid(VPA)monotherapy in epileptic patients.Methods 155 epileptic patients with VPA monotherapy were included for this study and a peripheral blood sample(4 mL)was collected from every participant.All patients were given oral administration VPA of 250-1500 mg·d^(-1) for the treatment of epilepsy and their seizure control status was followed up over 12 months.And a total of 138 patients were followed,among which 99 were divided into the response group and 39 into the nonresponse group according to seizure control status.Genotyping of 14 selected SNPs in miRNA genes was performed using the Agena MassARRAY platform.And the chi-square test was conducted for assessing the relationship between VPA efficacy and miRNA gene polymorphisms.Results The GA genotype frequency of MIR5090 rs3823658 in the response group was higher compared with the nonresponse group(30.61%vs.13.51%,P<0.05),and binary logistic regression equation showed that GA genotype was a protective factor for the efficacy of VPA(OR=3.187,P<0.05),which can explain 6.2%individual difference.And the genotype distributions of MIR8063 rs7183051 dominant model were statistically different in response group and nonresponse group(P<0.05)with a higher GA+AA frequency in the former group(31.96%vs.15.38%,P<0.05).No correlation with the efficacy of VPA was found in the other SNPs.Conclusion GA genotype of MIR5090 rs3823658 appears to be a protective factor for the efficacy of VPA in epileptic patients.

关 键 词：MICRORNA 丙戊酸 基因多态性 癫痫 疗效 

分 类 号：R97[医药卫生—药品]