MDR-1 and MRP2 Gene Polymorphisms in Mexican Epileptic Pediatric Patients with Complex Partial Seizures

Abstract

Although the Pgp efflux transport protein is overexpressed in resected tissue of patients with epilepsy, the presence of polymorphisms in MDR1/ABCB1 and MRP2/ABCC2 in patients with antiepileptic-drugs resistant epilepsy (ADR) is controversial. The aim of this study was to perform an exploratory study to identify nucleotide changes and search new and reported mutations in patients with ADR and patients with good response (CTR) to antiepileptic drugs (AEDs) in a rigorously selected population. We analyzed 22 samples In Material and Methods, from drug-resistant patients with epilepsy and 7 samples from patients with good response to AEDs. Genomic DNA was obtained from leukocytes. Eleven exons in both genes were genotyped. The concentration of drugs in saliva and plasma was determined. The concentration of valproic acid in saliva was lower in ADR than in CRT. In ABCB1, five reported SNPs and five unreported nucleotide changes were identified; rs2229109 (GA) and rs2032582 (AT and AG) were found only in the ADR. Of six SNPs associated with the ABCC2 that were found in the study population, rs3740066 (TT) and 66744T > A (TG) were found only in the ADR. The strongest risk factor in the ABCB1 gene was identified as the TA genotype of rs2032582, whereas for the ABCC2 gene the strongest risk factor was the T allele of rs3740066. The screening of SNPs in ACBC1 and ABCC2 indicates that the Mexican patients with epilepsy in this study display frequently reported ABCC1 polymorphisms; however, in the study subjects with a higher risk factor for drug resistance, new nucleotide changes were found in the ABCC2 gene. Thus, the population of Mexican patients with AED-resistant epilepsy (ADR) used in this study exhibits genetic variability with respect to those reported in other study populations; however, it is necessary to explore this polymorphism in a larger population of patients with ADR.

Association between the polymorphisms in the ATP-binding cassette genes ABCB1 and ABCC2 and the risk of drug-resistant epilepsy in a Chinese Han population

“…Several previous studies have reported an association between the ABCC2 rs2273697 and rs717620 polymorphisms and risk of drug-resistant epilepsy, but with conflicting results (Seo et al, 2008;Kwan et al, 2011;Hilger et al, 2012;Qu et al, 2012;Sporis et al, 2013;Subenthiran et al, 2013a;Escalante-Santiago et al, 2014;Ma et al, 2014). Qu et al (2012) revealed a significant association between the ABCC2 rs2273697 and rs717620 polymorphisms and resistance to antiepileptic drugs in Chinese epileptic patients.…”

The Association of OTX1 rs17850223 Polymorphisms in Han Chinese Patients with Idiopathic Epilepsy

“…Epilepsy is a leading neurologic condition triggered by the disruption of abnormal electrochemical activities in the brain. Idiopathic epilepsy, with no apparent structural brain damage or neurologic abnormality, is mainly caused by genetic factors [4][5][6]. The OTX1 gene encodes a member of the bicoid subfamily of homeodomain-containing transcription factors.…”

“…This disorder affects about 50 million people worldwide, and idiopathic epilepsy represents the majority of all epileptic seizure disorders [1][2][3]. There is increasing evidence that demonstrates genetic factors play a crucial role in the development of idiopathic epilepsy; these findings are mostly based on epidemiological studies, including those of familial aggregation, monozygotic twins, and families with a history of epilepsy [4][5][6].…”

Role of ABC-Transporters in Epileptogenesis and Pharmacoresistant Epilepsy

“…To date, all scientific literature indicates controversial results, where several studies suggest a positive relationship and several others indicate the opposite. A trend showing a negative correlation appears to be observed in caucasian cases [60][61][62], and a positive correlation in Mexican or Asiatic patients [56][57][58][59].…”