Effects of ABCB1 polymorphisms on plasma carbamazepine concentrations and pharmacoresistance in Chinese patients with epilepsy

被引:70
作者
Meng, Hongmei [2 ]
Guo, Guimei [2 ]
Ren, Jinyan [2 ]
Zhou, Hui [1 ]
Ge, Yubin [1 ,3 ,4 ]
Guo, Yingjie [1 ]
机构
[1] Jilin Univ, Coll Life Sci, Changchun 130023, Peoples R China
[2] Jilin Univ, Hosp 1, Changchun 130023, Peoples R China
[3] Wayne State Univ, Sch Med, Dev Therapeut Program, Barbara Ann Karmanos Canc Inst, Detroit, MI USA
[4] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA
关键词
Epilepsy; Carbamazepine; Polymorphism; Pharmacoresistance; Pharmacogenomics; DRUG-RESISTANT EPILEPSY; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; C3435T POLYMORPHISM; REFRACTORY EPILEPSY; ANTIEPILEPTIC DRUGS; MDR1; GENE; ASSOCIATION; EXPRESSION; HAPLOTYPE;
D O I
10.1016/j.yebeh.2011.02.015
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
P-glycoprotein may play a role in drug resistance in epilepsy by limiting gastrointestinal absorption and brain access of antiepileptic drugs (AEDs). We sought to investigate the effects of ABCB1 polymorphisms on plasma carbamazepine (CBZ) concentrations and pharmacoresistance in Chinese patients with epilepsy. C1236T, G2677T/A, and C3435T polymorphisms of ABCB1 were genotyped by polymerase chain reaction amplification followed by restriction fragment length polymorphism analysis or direct automated DNA sequencing in 84 patients treated with CBZ monotherapy. Patients with 3435-TT (n = 15) had lower adjusted CBZ concentrations than those with 3435-CC (n = 30) (P = 0.026). However there were no associations between all the studied genotypes, haplotypes, or diplotypes involving ABCB1 C1236T, G2677T/A, and C3435T polymorphisms and pharmacoresistance in the patient cohort. Our results suggest that ABCB1 3435-TT is associated with decreased plasma CBZ levels in Chinese patients with epilepsy. However, whether this contributes to CBZ resistance needs to be further investigated in a larger cohort of patients. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:27 / 30
页数:4
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