Analysis of Genotype and Haplotype Effects of ABCB1 (MDR1) Polymorphisms in the Risk of Medically Refractory Epilepsy in an Indian Population

Abstract

The transmembrane P-glycoprotein that functions as a drug-efflux transporter coded by ATP-binding cassette, subfamily B, member 1/Multidrug Resistance 1 (ABCB1/MDR1) gene is considered relevant to drug absorption and elimination, with access to the central nervous system. Effects of three ABCB1 single nucleotide polymorphisms (SNPs) in genotypic and haplotypic combination have been evaluated in a south Indian population for risk of pediatric medically refractory epilepsy. The study included age and sex matched medically refractory (N=113) cases and drug responsive epilepsy patients (N=129) as controls, belonging to the same ethnic population recruited from a tertiary referral centre, of Karnataka, Southern India. The genotype frequencies of SNPs c.1236C>T, c.2677G>T/A, and c.3435C>T were determined from genomic DNA of the cases and controls by PCR- RFLP and confirmatory DNA sequencing. 256 normal population samples of the same ethnicity were genotyped for the three loci to check for population stratification. Results indicate that there was no statistically significant difference between allele and genotype frequencies of refractory and drug responsive epilepsy patients. The predicted haplotype frequencies of the three polymorphisms did not show significant difference between cases and controls. The results confirm earlier observations on absence of association of ABCB1 polymorphisms with medically refractory epilepsy.

ABCB1 gene polymorphisms is not associated with drug-resistant epilepsy in Romanian children

“…[30] Many researchers have been concerned with the genotypic effects of these polymorphisms on drug resistance in epilepsy. The conflicting reports of several studies on genotype and allele frequency may be due to ethnic differences, knowing that gene polymorphisms often vary among ethnic groups, thus affecting the result of genetic studies.…”

SCN1A and ABCB1 Polymorphisms in Epilepsy

“…A coding SNP (cSNP), 3435C > T (rs1045642), in the ABCB1 gene was screened by a published PCR-RFLP method (8). To ensure the accuracy of the PCR-RFLP and ARMS-PCR methods, parts of the samples (about 15%) were randomly rechecked by direct sequencing.…”

“…On the other hand, a well known polymorphism (rs1045642 C > T) in exon 26 of the MDR1 gene that induces the transport of antiepileptic drugs shows clinical associations with drug resistance (6,8,9). It is proposed that a multigeneic interaction between the genes involved in both ABCB1 as well as the SCN1A genes could lead to a pharmaco-resistance to the AEDs (6,7,10,11).…”

Common ABCB1 polymorphisms associated with susceptibility to infantile spasms in the Chinese Han population

“…Of the patients with symptomatic etiology, 80 to 95% have mental retardation, compared with 30-50% for patients with cryptogenic infantile spasms (Riikonen, 2004;Tsao, 2009). Subgroup analyses of epilepsy syndrome have not been described in reports of most previous similar studies, which tend to include all epilepsy patients as a single cohort, with the finding of a negative association between drug responsiveness and C3435T polymorphisms (Kim et al, 2006;Vahab et al, 2009). The main aim of our study was to identify the pattern of ABCB1 genetic markers in children with infantile spasms.…”