影响丙戊酸药效的相关基因多态性研究进展
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摘要
丙戊酸是目前临床上广泛应用的抗癫药物之一,治疗多种类型的癫发作有效。但丙戊酸在临床应用中发现其疗效和不良反应均存在极大的个体差异。近年来研究提示,基因多态性可能是导致个体差异的原因之一。文中就药物代谢、效应通路和不良反应对影响丙戊酸药效的相关基因多态性研究进行归纳和总结。以期为临床个体化用药和精准治疗提供参考。
Valproic acid is one of the most widely used anti-epileptic drugs in the clinical,which is effective for various types of epilepsy and seizures. However,during valproic acid treatment,it remains difficult to predict the patients' individual response to the treatment. Recent studies suggest that genetic polymorphism may be one of the causes of this individual difference. In this review,a large number of candidate genes,which influence the efficacy and safety of valproic acid,are discussed from the aspects of drug metabolism,effector pathway and adverse reactions in order to provide reference for personalized medicine.
Valproic acid is one of the most widely used anti-epileptic drugs in the clinical,which is effective for various types of epilepsy and seizures. However,during valproic acid treatment,it remains difficult to predict the patients' individual response to the treatment. Recent studies suggest that genetic polymorphism may be one of the causes of this individual difference. In this review,a large number of candidate genes,which influence the efficacy and safety of valproic acid,are discussed from the aspects of drug metabolism,effector pathway and adverse reactions in order to provide reference for personalized medicine.
引文
[1]Ghodke-Puranik Y,Thorn CF,Lamba JK,et al.Valproic acid pathway:pharmacokinetics and pharmacodynamics[J].Pharmacogenet Genomics,2013,23:236-241
[2]Li X,Zhang J,Wu X,et al.Polymorphisms of ABAT,SCN2Aand ALDH5A1 may affect valproic acid responses in the treatment of epilepsy in Chinese[J].Pharmacogenomics,2016,17:2007-2014
[3]Haerian BS,Baum L,Kwan P,et al.SCN1A,SCN2A and SCN3A gene polymorphisms and responsiveness to antiepileptic drugs:a multicenter cohort study and meta-analysis[J].Pharmacogenomics,2013,14:1153-1166
[4]Lakhan R,Kumari R,Misra UK,et al.Differential role of sodium channels SCN1A and SCN2A gene polymorphisms with epilepsy and multiple drug resistance in the north Indian population[J].Br J Clin Pharmacol,2009,68:214-220
[5]Lv N,Qu J,Long H,et al.Association study between polymorphisms in the CACNA1A,CACNA1C,and CACNA1Hgenes and drug-resistant epilepsy in the Chinese Han population[J].Seizure,2015,30:64-69
[6]陆瑶,吴洵昳,王剑虹,等.亚洲人群UDP-葡萄糖醛酸转移酶基因多态性与药物代谢的相关性研究进展[J].中国临床神经科学,2016,24:579-586
[7]Hung CC,Ho JL,Chang WL,et al.Association of genetic variants in six candidate genes with valproic acid therapy optimization[J].Pharmacogenomics,2011,12:1107-1117
[8]Guo Y,Hu C,He X,et al.Effects of UGT1A6,UGT2B7,and CYP2C9 genotypes on plasma concentrations of valproic acid in Chinese children with epilepsy[J].Drug Metab Pharmacokinet,2012,27:536-542
[9]Chatzistefanidis D,Lazaros L,Giaka K,et al.UGT1A6-and UGT2B7-related valproic acid pharmacogenomics according to age groups and total drug concentration levels[J].Pharmacogenomics,2016,17:827-835
[10]Liu L,Zhao L,Wang Q,et al.Influence of valproic acid concentration and polymorphism of UGT1A4*3,UGT2B7-161C>T and UGT2B7*2 on serum concentration of lamotrigine in Chinese epileptic children[J].Eur J Clin Pharmacol,2015.71:1341-1347
[11]Wang Q,Zhao L,Liang M,et al.Effects of UGT2B7 Genetic Polymorphisms on Serum Concentrations of Valproic Acid in Chinese Children With Lamotrigine[J].Ther Drug Monit,2016.38:343-349
[12]Sun YX,Zhuo WY,Lin H,et al.The influence of UGT2B7genotype on valproic acid pharmacokinetics in Chinese epilepsy patients[J].Epilepsy Res,2015,114:78-80
[13]Wang P,Lin XQ,Cai WK,et al.Effect of UGT2B7 genotypes on plasma concentration of valproic acid:a meta-analysis[J].Eur J Clin Pharmacol,2018,74:433-422
[14]Chu XM,Zhang LF,Wang GJ,et al.Influence of UDP-glucuronosyltransferase polymorphisms on valproic acid pharmacokinetics in Chinese epilepsy patients[J].Eur J Clin Pharmacol,2012,68:1395-1401
[15]陈卓佳,王雪丁,王红胜,等.代谢相关基因多态性与丙戊酸所致不良反应的相关性研究[C].第十三次全国临床药理学学术大会论文集,2012:159-164
[16]Tan L,Yu JT,Sun YP,et al.The influence of cytochrome oxidase CYP2A6,CYP2B6,and CYP2C9 polymorphisms on the plasma concentrations of valproic acid in epileptic patients[J].Clin Neurol Neurosurg,2010,112:320-323
[17]Büdi T,Tóth K,Nagy A,et al.Clinical significance of CYP2C9-status guided valproic acid therapy in children[J].Epilepsia,2015,56:849-855
[18]廖清船,史菁菁,张永,等.细胞色素P450酶2A6、2B6、2C9及2C19基因多态性对丙戊酸钠血药浓度的影响[J].中华神经科杂志,2013,46:82-86
[19]Nanau RM,Neuman MG.Adverse drug reactions induced by valproic acid[J].Clin Biochem,2013,46:1323-1338
[20]Saneto RP,Cohen BH,Copeland WC,et al.AlpersHuttenlocher syndrome[J].Pediatr Neurol,2013,48:167-178
[21]Anagnostou ME,Ng YS,Taylor RW,et al.Epilepsy due to mutations in the mitochondrial polymerase gamma(POLG)gene:A clinical and molecular genetic review[J].Epilepsia,2016,57:1531-1545
[22]Stewart JD,Horvath R,Baruffini E,et al.Polymeraseγgene POLG determines the risk of sodium valproate-induced liver toxicity[J].Hepatology,2010,52:1791-1796
[23]Hynynen J,Komulainen T,Tukiainen E,et al.Acute liver failure after valproate exposure in patients with POLG1 mutations and the prognosis after liver transplantation[J].Liver Transpl,2014,20:1402-1412
[24]Fukushima Y,Seo T,Hashimoto N,et al.Glutathione-S-transferase(GST)M1 null genotype and combined GSTM1 and GSTT1 null genotypes are risk factors for increased serumγ-glutamyltransferase in valproic acid-treated patients[J].Clin Chim Acta,2008,389:98-102
[25]Saruwatari J,Deguchi M,Yoshimori Y,et al.Superoxide dismutase 2 Val16Ala polymorphism is a risk factor for the valproic acid-related elevation of serum aminotransferases[J].Epilepsy Res,2012,99:183-186
[2]Li X,Zhang J,Wu X,et al.Polymorphisms of ABAT,SCN2Aand ALDH5A1 may affect valproic acid responses in the treatment of epilepsy in Chinese[J].Pharmacogenomics,2016,17:2007-2014
[3]Haerian BS,Baum L,Kwan P,et al.SCN1A,SCN2A and SCN3A gene polymorphisms and responsiveness to antiepileptic drugs:a multicenter cohort study and meta-analysis[J].Pharmacogenomics,2013,14:1153-1166
[4]Lakhan R,Kumari R,Misra UK,et al.Differential role of sodium channels SCN1A and SCN2A gene polymorphisms with epilepsy and multiple drug resistance in the north Indian population[J].Br J Clin Pharmacol,2009,68:214-220
[5]Lv N,Qu J,Long H,et al.Association study between polymorphisms in the CACNA1A,CACNA1C,and CACNA1Hgenes and drug-resistant epilepsy in the Chinese Han population[J].Seizure,2015,30:64-69
[6]陆瑶,吴洵昳,王剑虹,等.亚洲人群UDP-葡萄糖醛酸转移酶基因多态性与药物代谢的相关性研究进展[J].中国临床神经科学,2016,24:579-586
[7]Hung CC,Ho JL,Chang WL,et al.Association of genetic variants in six candidate genes with valproic acid therapy optimization[J].Pharmacogenomics,2011,12:1107-1117
[8]Guo Y,Hu C,He X,et al.Effects of UGT1A6,UGT2B7,and CYP2C9 genotypes on plasma concentrations of valproic acid in Chinese children with epilepsy[J].Drug Metab Pharmacokinet,2012,27:536-542
[9]Chatzistefanidis D,Lazaros L,Giaka K,et al.UGT1A6-and UGT2B7-related valproic acid pharmacogenomics according to age groups and total drug concentration levels[J].Pharmacogenomics,2016,17:827-835
[10]Liu L,Zhao L,Wang Q,et al.Influence of valproic acid concentration and polymorphism of UGT1A4*3,UGT2B7-161C>T and UGT2B7*2 on serum concentration of lamotrigine in Chinese epileptic children[J].Eur J Clin Pharmacol,2015.71:1341-1347
[11]Wang Q,Zhao L,Liang M,et al.Effects of UGT2B7 Genetic Polymorphisms on Serum Concentrations of Valproic Acid in Chinese Children With Lamotrigine[J].Ther Drug Monit,2016.38:343-349
[12]Sun YX,Zhuo WY,Lin H,et al.The influence of UGT2B7genotype on valproic acid pharmacokinetics in Chinese epilepsy patients[J].Epilepsy Res,2015,114:78-80
[13]Wang P,Lin XQ,Cai WK,et al.Effect of UGT2B7 genotypes on plasma concentration of valproic acid:a meta-analysis[J].Eur J Clin Pharmacol,2018,74:433-422
[14]Chu XM,Zhang LF,Wang GJ,et al.Influence of UDP-glucuronosyltransferase polymorphisms on valproic acid pharmacokinetics in Chinese epilepsy patients[J].Eur J Clin Pharmacol,2012,68:1395-1401
[15]陈卓佳,王雪丁,王红胜,等.代谢相关基因多态性与丙戊酸所致不良反应的相关性研究[C].第十三次全国临床药理学学术大会论文集,2012:159-164
[16]Tan L,Yu JT,Sun YP,et al.The influence of cytochrome oxidase CYP2A6,CYP2B6,and CYP2C9 polymorphisms on the plasma concentrations of valproic acid in epileptic patients[J].Clin Neurol Neurosurg,2010,112:320-323
[17]Büdi T,Tóth K,Nagy A,et al.Clinical significance of CYP2C9-status guided valproic acid therapy in children[J].Epilepsia,2015,56:849-855
[18]廖清船,史菁菁,张永,等.细胞色素P450酶2A6、2B6、2C9及2C19基因多态性对丙戊酸钠血药浓度的影响[J].中华神经科杂志,2013,46:82-86
[19]Nanau RM,Neuman MG.Adverse drug reactions induced by valproic acid[J].Clin Biochem,2013,46:1323-1338
[20]Saneto RP,Cohen BH,Copeland WC,et al.AlpersHuttenlocher syndrome[J].Pediatr Neurol,2013,48:167-178
[21]Anagnostou ME,Ng YS,Taylor RW,et al.Epilepsy due to mutations in the mitochondrial polymerase gamma(POLG)gene:A clinical and molecular genetic review[J].Epilepsia,2016,57:1531-1545
[22]Stewart JD,Horvath R,Baruffini E,et al.Polymeraseγgene POLG determines the risk of sodium valproate-induced liver toxicity[J].Hepatology,2010,52:1791-1796
[23]Hynynen J,Komulainen T,Tukiainen E,et al.Acute liver failure after valproate exposure in patients with POLG1 mutations and the prognosis after liver transplantation[J].Liver Transpl,2014,20:1402-1412
[24]Fukushima Y,Seo T,Hashimoto N,et al.Glutathione-S-transferase(GST)M1 null genotype and combined GSTM1 and GSTT1 null genotypes are risk factors for increased serumγ-glutamyltransferase in valproic acid-treated patients[J].Clin Chim Acta,2008,389:98-102
[25]Saruwatari J,Deguchi M,Yoshimori Y,et al.Superoxide dismutase 2 Val16Ala polymorphism is a risk factor for the valproic acid-related elevation of serum aminotransferases[J].Epilepsy Res,2012,99:183-186