UGT1A6、UGT1A9基因多态性对丙戊酸血药浓度-体重日剂量比值的影响
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- 英文论文题名：Effect of UGT1A6 and UGT1A9 gene polymorphisms on plasma concentration-to-dose ratio of valproic acid
- 论文作者：林雪玉 ; 张燕青 ; 林鹏锋 ; 周凯琴 ; 洪惠 ; 费燕
- 英文论文作者：LIN Xue-Yu ; ZHANG Yan-Qing ; LIN Peng-Feng ; ZHOU Kai-Qin ; HONG Hui ; FEI Yan ; Department of Pharmacy ; NO.175 Hospital of PLA
- 年：2016
- 作者机构：解放军第175医院药学科;
- 论文关键词：丙戊酸 ; UGT1A6 ; UGT1A9 ; 基因多态性 ; 癫痫
- 英文论文关键词：valproic acid ; UGTIA9 ; UGTIA6 ; polymorphism ; epileptic
- 会议召开时间：2016-09-27
- 会议录名称：中国药学会第十三届青年药学科研成果交流会论文集
- 语种：中文
- 分类号：R969
- 学会代码：YYWS
- 会议名称：中国药学会第十三届青年药学科研成果交流会
- 会议地点：中国江西南昌
- 主办单位：中国药学会
- 学会名称：中国药学会
- 页数：5
- 文件大小：316k
- 原文格式：O
- 会议级别：全国
摘要
目的:考察尿苷二磷酸葡萄糖醛酸转移酶(UGT)1A6和1A9的单核苷酸多态性(SNP)与癫痫患者丙戊酸血药浓度之间的相关性。方法:共纳入107例丙戊酸单药抗癫痫治疗的中国癫痫患者,采用酶免疫增强放大法(EMIT)检测丙戊酸血浆稳态谷浓度。采用Sequenom(?)MassARRAY system对UGT1A6(rs2070959,rs6759892)和UGT1A9(rs13418420,rs2741045,rs2741049,rs6731242,rs72551330)进行基因分型,并分析上述基因型对丙戊酸血药浓度-体重日剂量比值(CDR)的影响。结果:UGT1A6rs6759892,rs2070959存在连锁不平衡(D′=1.000;r~2=0.934)。UGT1A6rs2070959,rs6759892携带突变基因组的丙戊酸CDR低于野生纯和组,差异有统计学意义(P<0.05)。结论:癫痫患者UGT1A6 rs2070959,rs6759892基因多态性与丙戊酸血药浓度相关,该基因型检测将有助于指导丙戊酸的临床个体化用药。
Objective:The study aims to investigate the associations of UGT1A6 and UGT1A9 polymorphisms with valproic acid plasma concentrations in Chinese epileptic patients.Methods:Blood samples and clinical data were collected from 107 epileptic patients with valproic acid monotherapy treatment.The concentration of valproic acid was detected by EMIT method.UGT1A6(rs2070959,rs6759892) and UGT1A9(rsl3418420,rs2741045,rs2741049,rs6731242,rs72551330)genotypes were detected by Sequenom(?) MassARRAY system.Results:UGT1A6 rs2070959,rs6759892 genotypes were in linkage disequilibrium(D'=1.000;r~2=0.934).Patients with variant genotypes in UGT1A6 rs6759892 and rs2070959 showed lower CDR of valproic acid than those with wild-types(P < 0.05).The results illustrated that UGT1A6 rsl3418420,rs2070959 polymorphisms were associated with valproic acid concentrations,and the test of these genotypes may be useful for individualized medicine of valproic acid.
Objective:The study aims to investigate the associations of UGT1A6 and UGT1A9 polymorphisms with valproic acid plasma concentrations in Chinese epileptic patients.Methods:Blood samples and clinical data were collected from 107 epileptic patients with valproic acid monotherapy treatment.The concentration of valproic acid was detected by EMIT method.UGT1A6(rs2070959,rs6759892) and UGT1A9(rsl3418420,rs2741045,rs2741049,rs6731242,rs72551330)genotypes were detected by Sequenom(?) MassARRAY system.Results:UGT1A6 rs2070959,rs6759892 genotypes were in linkage disequilibrium(D'=1.000;r~2=0.934).Patients with variant genotypes in UGT1A6 rs6759892 and rs2070959 showed lower CDR of valproic acid than those with wild-types(P < 0.05).The results illustrated that UGT1A6 rsl3418420,rs2070959 polymorphisms were associated with valproic acid concentrations,and the test of these genotypes may be useful for individualized medicine of valproic acid.
引文
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[3]Amitava Dasgupta(著),陆林(译).药物监测方法:治疗性用药与药物滥用[M].北京:人民卫生出版社,2011.
[4]Tan L,Yu J T,Sun Y P,et al.The influence of cytochrome oxidase CYP2A6,CYP2B6,and CYP2C9 polymorphisms on the plasma concentrations of valproic acid in epileptic patients[J].Clinical Neurology&Neurosurgery,2010,112(4):320-323.
[5]Sun YP,Tan L,Wang Y,et al.Effect of UGT1A6 genetic polymorphisms on the metabolism of sodium valproate[J].Zhonghua Yi Xue Za Zhi 2007,87,2033-2035.
[6]Chu X M,Zhang L F,Wang G J,et al.Influence of UDP-glucuronosyltransferase polymorphisms on valproic acid pharmacokinetics in Chinese epilepsy patients.[J].European Journal of Clinical Pharmacology,2012,68(10):1395-1401.
[7]Jiang D,Bai X,Zhang Q,et al.Effects of CYP2C19 and CYP2C9 genotypes on pharmacokinetic variability of valproic acid in Chinese epileptic patients:nonlinear mixed-effect modeling[J].European Journal of Clinical Pharmacology,2009,65(12):1187-93.
[8]Johannessen C U,Johannessen S I.Valproate:Past,Present,and Future[J].Cns Drug Reviews,2003,9(2):199-216.
[9]HUNG C C,HO J L,CHANG W L,et al.Association of genetic variants in six candidate genes with valproic acid therapy optimization[J].Pharmacogenomics,2011,12(8):1107-1117.
[10]Shi YY,He L.SHEsis,a powerful software platform for analyses of linkage disequilibrium,haplotype construction,and genetic association at polymorphism loci[J].Cell Res.2005 Feb;15(2):97-8.
[11]Yogita Ghodke-Puranik,Caroline F.Thornd,Jatinder K.Lamba et al,Valproic acid pathway:pharmacokinetics and pharmacodynamics[J].Pharmacogenet Genom.2013 April;23(4):236-241.
[12]Argikar U A,Remmel R P.Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4,UGT1A8,and UGT1 A10.[J].Drug Metabolism&Disposition the Biological Fate of Chemicals,2009,37(1):229-36.
[13]https://www.ncbi.nlm.nih.gov/projects/SNP/snp_summary.cgi
[2]Terbach N,Williams RS.Structure-function studies for the panacea,valproic acid[J].Biochem Soc Trans,2009,37(Pt 5):1126-1132.
[3]Amitava Dasgupta(著),陆林(译).药物监测方法:治疗性用药与药物滥用[M].北京:人民卫生出版社,2011.
[4]Tan L,Yu J T,Sun Y P,et al.The influence of cytochrome oxidase CYP2A6,CYP2B6,and CYP2C9 polymorphisms on the plasma concentrations of valproic acid in epileptic patients[J].Clinical Neurology&Neurosurgery,2010,112(4):320-323.
[5]Sun YP,Tan L,Wang Y,et al.Effect of UGT1A6 genetic polymorphisms on the metabolism of sodium valproate[J].Zhonghua Yi Xue Za Zhi 2007,87,2033-2035.
[6]Chu X M,Zhang L F,Wang G J,et al.Influence of UDP-glucuronosyltransferase polymorphisms on valproic acid pharmacokinetics in Chinese epilepsy patients.[J].European Journal of Clinical Pharmacology,2012,68(10):1395-1401.
[7]Jiang D,Bai X,Zhang Q,et al.Effects of CYP2C19 and CYP2C9 genotypes on pharmacokinetic variability of valproic acid in Chinese epileptic patients:nonlinear mixed-effect modeling[J].European Journal of Clinical Pharmacology,2009,65(12):1187-93.
[8]Johannessen C U,Johannessen S I.Valproate:Past,Present,and Future[J].Cns Drug Reviews,2003,9(2):199-216.
[9]HUNG C C,HO J L,CHANG W L,et al.Association of genetic variants in six candidate genes with valproic acid therapy optimization[J].Pharmacogenomics,2011,12(8):1107-1117.
[10]Shi YY,He L.SHEsis,a powerful software platform for analyses of linkage disequilibrium,haplotype construction,and genetic association at polymorphism loci[J].Cell Res.2005 Feb;15(2):97-8.
[11]Yogita Ghodke-Puranik,Caroline F.Thornd,Jatinder K.Lamba et al,Valproic acid pathway:pharmacokinetics and pharmacodynamics[J].Pharmacogenet Genom.2013 April;23(4):236-241.
[12]Argikar U A,Remmel R P.Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4,UGT1A8,and UGT1 A10.[J].Drug Metabolism&Disposition the Biological Fate of Chemicals,2009,37(1):229-36.
[13]https://www.ncbi.nlm.nih.gov/projects/SNP/snp_summary.cgi
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