No association of ABCB1 polymorphisms with drug-refractory epilepsy in a north Indian population

被引:64
作者
Lakhan, R. [1 ]
Misra, U. K. [2 ]
Kalita, J. [2 ]
Pradhan, S. [2 ]
Gogtay, N. J. [3 ,4 ]
Singh, M. K. [5 ]
Mittal, B. [1 ]
机构
[1] Sanjay Gandhi Postgrad Inst Med Sci, Dept Genet, Lucknow 226014, Uttar Pradesh, India
[2] Sanjay Gandhi Postgrad Inst Med Sci, Dept Neurol, Lucknow 226014, Uttar Pradesh, India
[3] GS Med Coll, Dept Clin Pharmacol, Bombay, Maharashtra, India
[4] King Edward Mem Hosp, Bombay, Maharashtra, India
[5] CSM Med Univ, Dept Neurol, Lucknow, Uttar Pradesh, India
关键词
ABCB1; Drug resistance; Epilepsy; Single-nucleotide polymorphism; SINGLE NUCLEOTIDE POLYMORPHISMS; MDR1; GENETIC-POLYMORPHISM; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; ANTIEPILEPTIC DRUGS; C3435T POLYMORPHISM; FREQUENCY;
D O I
10.1016/j.yebeh.2008.08.019
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
Multiple drug resistance is a common problem in the treatment of epilepsy, and approximately 30% of patients continue to have seizures despite all therapeutic interventions. Among various classes of drug transporters, genetic variants of P-glycoprotein (P-gp) encoded by the ABCB1 (ATP-binding cassette subfamily B member 1) gene have been associated with drug-refractory epilepsy. Our aim was to investigate the effect of the 1236C>T(rs1128503), 2677G>T/A(rs2032582), and 3435C>T(rs1045642) single-nucleotide polymorphisms of ABCB1 (or MDR1) on drug resistance in north Indian patients with epilepsy. Genotyping was performed in 101 control Subjects and 325 patients with epilepsy, of whom 94 were drug resistant and 231 drug responsive. Therapeutic drug monitoring for phenytoin, carbamazepine, phenobarbital, and valproate was also performed to confirm compliance in 20% of the patients. Genotype and haplotype frequencies of these polymorphisms did not differ between drug-resistant and drug-responsive patients. Our results demonstrate ABCB1 polymorphisms are not associated with drug resistance in north Indian epileptic patients. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:78 / 82
页数:5
相关论文
共 28 条
[1]   Frequency of C3435T single nucleotide MDR1 genetic polymorphism in an Asian population: phenotypic-genotypic correlates [J].
Balram, C ;
Sharma, A ;
Sivathasan, C ;
Lee, EJD .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2003, 56 (01) :78-83
[2]   Defining intractability: Comparisons among published definitions [J].
Berg, AT ;
Kelly, MM .
EPILEPSIA, 2006, 47 (02) :431-436
[3]   Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects [J].
Cascorbi, I ;
Gerloff, T ;
Johne, A ;
Meisel, C ;
Hoffmeyer, S ;
Schwab, M ;
Schaeffeler, E ;
Eichelbaum, M ;
Brinkmann, U ;
Roots, I .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2001, 69 (03) :169-174
[4]  
CHANTAL D, 2006, EUR J PAEDIATR NEURO, V10, P57
[5]   Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy [J].
Dombrowski, SM ;
Desai, SY ;
Marroni, M ;
Cucullo, L ;
Goodrich, K ;
Bingaman, W ;
Mayberg, MR ;
Bengez, L ;
Janigro, D .
EPILEPSIA, 2001, 42 (12) :1501-1506
[6]   Genotype and allele frequencies of TPMT, NAT2, GST, SULT1A1 and MDR-1 in the Egyptian population [J].
Hamdy, SI ;
Hiratsuka, M ;
Narahara, K ;
Endo, N ;
El-Enany, M ;
Moursi, N ;
Ahmed, MSE ;
Mizugaki, M .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2003, 55 (06) :560-569
[7]   Complex haplotypic effects of the ABCB1 gene on epilepsy treatment response [J].
Hung, CC ;
Tai, JJ ;
Lin, CJ ;
Lee, MJ ;
Liou, HH .
PHARMACOGENOMICS, 2005, 6 (04) :411-417
[8]   Association of polymorphisms in NR1I2 and ABCB1 genes with epilepsy treatment responses [J].
Hung, Chin-Chuan ;
Tai, John Jen ;
Kao, Pi-Ju ;
Lin, Min-Sbung ;
Liou, HornHuei .
PHARMACOGENOMICS, 2007, 8 (09) :1151-1158
[9]   Lack of association between C3435T nucleotide MDR1 genetic polymorphism and multidrug-resistant epilepsy [J].
Kim, Dong Wook ;
Kim, Manho ;
Lee, Sang Kun ;
Kang, Rami ;
Lee, Seo-Young .
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY, 2006, 15 (05) :344-347
[10]   Single nucleotide polymorphisms in the multidrug resistance 1 gene in Korean epileptics [J].
Kim, YO ;
Kim, MK ;
Woo, YJ ;
Lee, MC ;
Kim, JH ;
Park, KW ;
Kim, EY ;
Roh, YI ;
Kim, CJ .
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY, 2006, 15 (01) :67-72