转运体基因多态性对癫痫患者丙戊酸血药浓度及临床疗效的影响  

Influence of transporter genetic polymorphisms on valproic acid blood concentration and clinical efficacy of epilepsy patients

作　　者：陈娟[1] 王雪丁[1] 周列民[2] 李宏亮[1] 周亚芳[1] 秦家明 戴启麟[2] 黄民[1] 

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

出　　处：《中国临床药理学杂志》2016年第3期215-217,共3页The Chinese Journal of Clinical Pharmacology

基　　金："十二五"国家科技重大专项资金资助项目(2012ZX09506001-004);国家自然科学基金资助项目(81320108027;81173131;81473283)

摘　　要：目的 考察丙戊酸（VPA）转运体ABCC2,MCT1,MCT2,OATP2B1的单核苷酸多态性（SNP）对癫痫患者丙戊酸稳态浓度和临床疗效的影响。方法 纳入160例单用丙戊酸控制1年以上癫痫患者,用高效液相色谱法测定丙戊酸稳态血药浓度,用Sequenom Mass ARRAY system对ABCC2 rs2273697,rs3740066,MCT1 rs60844753,rs7169,MCT2 rs10784000,rs10877333,rs1693614,OATP2B1rs2306168进行基因分型,分析上述基因型对丙戊酸浓度和临床疗效的影响。结果 ABCC2 rs2273697（1249G〉A）AA型患者的丙戊酸血药浓度显著高于GA型和GG型（P〈0.05）,其它SNPs各基因型对丙戊酸体重剂量校正浓度和临床疗效无显著影响。结论 ABCC2 rs2273697与丙戊酸血药浓度相关,该基因型对丙戊酸浓度和临床疗效的影响需进一步扩大样本量考察。Objective To investigate the effect of ABCC2, MCT1, MCT2, OATP2B1 on valproic acid （VPA） blood concentration and effi- cacy in epilepsy patients. Methods One hundred sixty epilepsy patients receiving VPA as monotherapy were included. Steady -state blood con- centration of VPA was measured by a high - performance liquid chroma- tography method. ABCC2 rs2273697, rs3740066, MCT1 rs60844753, rs7169, MCT2 rs10784000, rs10877333, rs1693614, OATP2B1 rs2306168 genotypes were detected by Sequenom Mass ARRAY ~ sys- tem. The association between different genotypes and VPA concentration was analyzed by Kruskal -Wallis test. Efficacy comparison among geno- types were performed by Chi - square test. Results The concentration of valproic acid in ABCC2 rs2273697 AA genotype was considerably higher than the GA and GG genotypes （P 〈 0.05）. There was no significant effect of other SNPs on VPA close - adjusted concentration and clinical efficacy. Conclusion ABCC2 rs2273697 polymorphism is associated with valproic acid blood concentrations, and further studies are needed to verify the effect of this SNP on VPA blood concentration and clinical efficacy.

关 键 词：丙戊酸 转运体 基因多态性 血药浓度 临床疗效 

分 类 号：R971.6[医药卫生—药品] R968[医药卫生—药学]