SLCO1A2、SLCO2B1及SLCO1B1的单核苷酸多态性与丙戊酸抗癫痫疗效的相关性研究  

Association of single nucleotide polymorphisms of SLCO1A2,SLCO2B1 and SLCO1B1 genes with the effectiveness of valproic acid in epileptic patients

作　　者：唐思媛 李蕊彤 陈子怡[2] 倪冠中[2] 任瑞娜 刘松泽 周列民[2] 王雪丁[1] 黄民[1] TANG Si-yuan;LI Rui-tong;CHEN Zi-yi;NI Guan-zhong;REN Rui-na;LIU Song-ze;ZHOU Lie-min;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,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》2023年第7期946-950,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(2020B1212060034)。

摘　　要：目的考察转运体基因溶质载体有机阴离子转运蛋白家族成员1A2(SLCO1A2)、SLCO2B1及SLCO1B1的单核苷酸多态性(SNPs)与丙戊酸抗癫痫疗效的相关性。方法纳入单用丙戊酸的癫痫患者,根据随访期内的发作控制情况将患者分为有效控制组和未有效控制组。用MassARRAY平台对患者SLCO1A2 rs4149000、SLCO2B1 rs2306168、SLCO2B1 rs12422149及SLCO1B1 rs4149056进行基因分型,分析不同基因型与丙戊酸抗癫痫疗效的关系。结果SLCO1A2 rs4149000 CC/CT+TT基因型在有效控制组和未有效控制组的分布分别为102/26和48/4;在共显性模型下,SLCO2B1 rs12422149 GG/GA/AA基因型在有效控制组和未有效控制组的分布分别为61/50/17和33/19/0;同时,SLCO1B1 rs4149056 TT/TC/CC基因型在有效控制组和未有效控制组的分布分别为92/32/4和48/4/0,以上基因型在有效控制组和未有效控制组中的分布差异均有统计学意义(均P<0.05)。其中,rs12422149和rs4149056被纳入多因素Logistic回归方程,rs12422149 GG型(OR=2.295,P<0.05)及rs4149056 TT型(OR=5.201,P<0.05)患者丙戊酸疗效较差,2个位点共同解释59.6%的丙戊酸耐药的个体差异。结论SLCO2B1 rs12422149野生型(GG型)和SLCO1B1 rs4149056野生型(TT型)更容易发生丙戊酸耐药。Objective To investigate the correlation between single nucleotide polymorphisms(SNPs)of SLCO1A2,SLCO2B1,and SLCO1B1 and the treatment effectiveness of epileptic patients with valproic acid(VPA)monotherapy.Methods Epileptic patients treated with valproic acid alone were included and divided into response group and nonresponse group according to the seizure control during the follow-up period.Genotyping of SLCO1A2 rs4149000,SLCO2B1 rs2306168,SLCO2B1 rs12422149 and SLCO1B1 rs4149056 was performed by using the MassARRAY platform.Assessment of the relationship between genotypes and effectiveness of valproic acid was conducted.Results In the dominant model,the distribution of SLCO1A2 rs4149000 CC/CT+TT genotypes in the response group and the nonresponse group was 102/26 and 48/4,respectively.In the co-dominant model,the distribution of SLCO2B1 rs12422149 GG/GA/AA genotype in the response group and the nonresponse group was 61/50/17 and 33/19/0,respectively.Meanwhile,the distribution of SLCO1B1 rs4149056 TT/TC/CC genotype in the response group and the nonresponsegroup was 92/32/4 and 48/4/0,respectively.The distribution of the above genotypes in the response group and thenonresponse group were significant different(all P<0.05).Moreover,SLCO2B1 rs12422149 and SLCO1B1 rs4149056were included in the multivariate logistic regression equation,where rs12422149 GG genotype and rs4149056 TTgenotype were both associated with worse effectiveness of valproic acid(OR=2.295,P<0.05,rs12422149;OR=5.201,P<0.05,rs4149056).Conclusion Patients with rs12422149 wildtype and rs4149056 wildtype may haveworse response to valproic acid treatment,which may provide a basis for individualized medication regimen of valproicacid.

关 键 词：丙戊酸 转运体 单核苷酸多态性 癫痫 疗效 

分 类 号：R971.6[医药卫生—药品]