ABCB1 C3435T基因多态性与新疆癫痫患儿左乙拉西坦血药浓度和临床疗效的相关性研究

doi:10.11669/cpj.2020.18.009

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (3211 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的初步探讨ABCB1 C3435T基因多态性是否影响新疆癫痫患儿口服左乙拉西坦(levetiracetam,LEV)后的血药浓度、临床疗效和不良反应。方法收集并测定116例口服LEV的新疆癫痫患儿血清药物浓度,采用聚合酶链反应-荧光染色原位杂交法检测其ABCB1 C3435T基因型,分析患儿ABCB1 C3435T基因多态性与其血药浓度、临床疗效与不良反应之间的相关性。结果患儿ABCB1 C3435T的C和T等位基因频率存在显著性差异(χ²=12.520, P<0.01)。CC型、CT型和TT型患儿的血药浓度结果分别为12.02、13.74和14.53 μg·mL^-1,方差分析结果显示,3组之间存在显著性差异(F=3.550,P<0.05)。携带TT型的新疆癫痫患儿LEV血药浓度明显高于CC型和CT型。CC型、CT型和TT型患儿的LEV治疗有效组和无效组的c_ss差异均无统计学意义(P>0.05)。CT型患儿的临床治疗有效率高于CC型和TT型患儿,TT型患儿的不良反应发生率高于CC型和CT型患儿。CC型、CT型和TT型患儿的临床疗效和不良反应存在显著性差异(χ²=12.870,P<0.01;χ²=19.292,P<0.01)。结论 ABCB1 C3435T基因多态性可能影响新疆癫痫患儿的LEV血药浓度结果、临床疗效和不良反应。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	赵婷
	于静
	王婷婷
	冯杰
	孙力
	孙岩
	于鲁海
	李红健

关键词 ： ABCB1 C3435T, 血药浓度, 左乙拉西坦

Abstract：OBJECTIVE To explore the relationship between multidrug resistance gene ABCB1 C3435T gene polymorphism and serum concentration, clinical efficacy and adverse reactions of levetiracetam (LEV) in children with epilepsy in Xinjiang. METHODS The serum concentration of 116 children with epilepsy of in Xinjiang were collected and determined by oral LEV. The ABCB1 C3435T genotype was detected by polymerase chain reaction-fluorescence staining in situ hybridization. The correlation between ABCB1 C3435T gene polymorphism and serum concentration, clinical efficacy and adverse reactions was analyzed. RESULTS The C and T allele frequencies of ABCB1 C3435T in children were significantly different (χ²=12.520, P<0.01). The serum concentration of CC, CT and TT genotypes were 12.02, 13.74 and 14.53 μg·mL^-1, respectively. The results of ANOVA showed that there were significant differences among the three groups (F=3.550,P<0.05). The serum concentration of LEV in children with epilepsy in Xinjiang with TT type was significantly higher than that of CC type and CT type. There was no significant difference in c_ss between LEV effective group and ineffective group in CC type, CT type and TT type(P>0.05). The clinical effective rate of CT type was higher than that of CC type and TT type, and the incidence of adverse reactions of TT type was higher than that of CC type and CT type. There were significant differences in clinical efficacy and adverse reactions among CC type, CT type and TT type (χ²=12.870,P<0.01; χ²=19.292, P<0.01). CONCLUSION ABCB1 C3435T gene polymorphism may has a effect on the serum concentration, clinical efficacy and adverse reactions of LEV in children with epilepsy in Xinjiang.

Key words： ABCB1 C3435T serum concentration levetiracetam

收稿日期: 2020-04-11

PACS:

R969.1

基金资助:中国抗癫痫协会癫痫科研基金-优时比基金项目资助(201804)

通讯作者: 李红健,男,主任药师研究方向:药物分析与临床药学 Tel:(0991)8562413 E-mail:leehongjian2006 @163.com

作者简介: 赵婷,女,硕士,主管药师研究方向:药物分析与临床药学

引用本文:

赵婷, 于静, 王婷婷, 冯杰, 孙力, 孙岩, 于鲁海, 李红健. ABCB1 C3435T基因多态性与新疆癫痫患儿左乙拉西坦血药浓度和临床疗效的相关性研究[J]. 中国药学杂志, 2020, 55(18): 1530-1534. ZHAO Ting, YU Jing, WANG Ting-ting, FENG Jie, SUN Li, SUN Yan, YU Lu-hai, LI Hong-jian. Relationship between Multidrug Resistance Gene ABCB1 C3435T Gene Polymorphism and Serum Concentration of Levetiracetam in Children with Epilepsy in Xinjiang. Chinese Pharmaceutical Journal, 2020, 55(18): 1530-1534.

链接本文:

http://journal11.magtechjournal.com/Jwk_zgyxzz/CN/10.11669/cpj.2020.18.009 或 http://journal11.magtechjournal.com/Jwk_zgyxzz/CN/Y2020/V55/I18/1530

[1]	SHEN X M, WANG W P. Pediatrics (儿科学) [M]. 7th Edition. Beijing: People′s Health Publishing House, 2008: 390-391.
[2]	HUGHES J R. One of the hottest topics in epileptology: ABC proteins. Their inhibition may be the future for patients with intractable seizures[J]. Neurol Res, 2008, 30(9):920-925.
[3]	CHOONG E, DOBRINAS M, CARRUPT P A, et al. The permeability P-glycoprotein: a focus on enantioselectivity and brain distribution[J]. Expert Opin Drug Metab Toxicol, 2010, 6(8):953-965.
[4]	CREPEAU A Z, TREIMAN D M. Levetiracetam:a comprehensive review[J]. Expert Rev Neurother, 2010, 10(2):159-171 .
[5]	KALOW W. Pharmacogenetics and pharmacogenomics: origin, status, and the hope for personalized medicine[J]. Pharmacogenomics, 2006, 6(3): 162-165.
[6]	GOLDSTEIN D B, NEED A C, SINGH R, et al. Potential genetic causes of heterogeneity of treatment effects[J]. Am J Med, 2007, 120 (4): 21-25.
[7]	TATE S K, SISODIYA S M. Multidrug resistance in epilepsy: a pharmacogenomic update[J]. Expert Opin Pharmacother, 2007, 8 (10): 1441-1449.
[8]	ZHENG X Z. Study on the relationship between Drug Resistance, Pharmacological Mechanism of levetiracetam and MDR1 C3435T Polymorphism in Refractory Epilepsy [D]. Tianjin Medical University, 2009.
[9]	ZHENG X Z, WU S J, XIA M, et al. Efficacy of levetiracetam in the treatment of refractory partial epilepsy and its association with multidrug resistance genes: a randomized double-blind placebo-controlled clinical trial[J]. Chin J Contemp Neurol Nearosur (中国现代神经疾病杂志), 2009,9(2): 173-177.
[10]	WANG T T, LI H J, JIA L, et al. Monitoring and analysis of plasma concentration of oxcarbazepine active metabolites in Uygur children with epilepsy[J]. Chin J Hosp Pharm(中国医院药学杂志), 2016, 35 (8): 645.
[11]	BEATRICE M, FRANCOISE V B. ABC multidrug transporters: target for modulation of drug pharmacokinetics and drug-drug interactions[J]. Current Drug Targets, 2011, 12(5):600-620.
[12]	PAUL Y. Various epileptic seizure detection techniques using biomedical signals: a review[J]. Brain Inform, 2018, 5(2):6.
[13]	KIM D W, LEE S K, CHU K, et al. Lack of association between ABCB1, ABCG2 and ABCC2 genetic polymorphisms and multidrug resistance in partial epilepsy[J]. Epilepsy Res, 2009, 84(1):86-90.
[14]	DERICIOGLU N,BABAOGLU M O, YASAR U, et al. Multidrug resistance in patients undergoing resective epilepsy surgery is not associated with C3435T polymorphism in the ABCB1 (MDR1) gene[J]. Epilepsy Res, 2008, 80(1): 42-46.
[15]	WEST C L, MEALEY K L. Assessment of antiepileptic drugs as substrates for canine P-glycoprotein[J]. Am J Vet Res, 2007, 68(10): 1106-1110.
[16]	CARLOS L T, MAREN F, WOLFGANG L. Several major antiepileptic drugs are substrates for human P-glycoprotein[J]. Neuropharm, 2008, 55(1): 1364-1375.
[17]	HUNG C C, CHEN C C, LIN C J, et al. Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs[J]. Original Article, 2008, 18(5): 390-402.
[18]	ZHANG Y T, ZHANG H, YANG L P, et al. Effect of ABCB1 and CYP3A5 gene polymorphisms on plasma cyclosporine concentration.[J]. Chin Pharm J (中国药学杂志), 2011, 46(5): 368-373.
[19]	FELDMANN M, ASSELIN M C, LIU J. P-glycoprotein expression and function in patients with temporal lobe epilepsy: a case-control study[J]. Lancet Neurol, 2013, 12(8): 777-785.
[20]	DONG W K, MANHO K, SANG K L, et al. Lack of association between C3435T nucleotide MDR1 genetic polymorphism and multidrug-resistant epilepsy[J]. Seizure, 2006,15(5): 344-347.
[21]	ZORAN S, GORDANA K T, EMILIJA C, et al. The association of C3435T single-nucleotide polymorphism, Pgp-glycoprotein gene expression levels and carbamazepine maintenance dose in patients with epilepsy[J]. Neuropsycheatric Dis Treat, 2012, 8(8):191-196.
[22]	SIDDIQUI A, KERB R, WESLE M E, et al. Association of multidrug resistance in epilepsy with a polymorphism in the drug- transporter dene ABCB1[J]. New Engl J Med, 2003, 348(15): 1442-1448.
[23]	SEO T, ISHITSU T, UEDA N, et al. ABCB1 polymorphisms influence the response to antiepileptic drugs in Japanese epilepsy patients[J]. Pharmacogenomics, 2006, 7(4): 551-561.
[24]	KWAN P, BAUM L, WONG V, et al. Association between ABCB1 C3435T polymorphism and drug-resistant epilepsy in Han Chinese[J]. Epilepsy Behavior, 2007, 11(1): 112-117.
[25]	DONG T, XU X R, ZHANG Q. Study on the relationship between ABCB1 C3435T and drug resistance in patients with epilepsy of Hui nationality in Ningxia[J]. J Ningxia Med Univ(宁夏医科大学学报), 2011, 33(2): 108-111.