| Backgrounds and ObjectiveEpilepsy is the most prevalent chronic neurological disorder, approximately60%of epileptics had their seizure initially from childhood. Although a majority of patients with epilepsy are responsive to the presently available antiepileptic drugs, nearly one-third of them continue to exhibit recurrent seizures, which is called refractory epilepsy. The introduction of several new AEDs in the recent years has not improved the outcome of these patients. Patients with drug-resistant epilepsies are physically and socially disabled, which has become a serious global public health problem.What are the causes of the forming to refractory epilepsy? is it because the body resistant to AEDs? Then, what is the mechanisms? To this end, the medical profession has made unremitting efforts.Recent studies showed that resistance to AED is considered as a complex phenomenon that may involve many mechanisms, none of which is well understood. Through the research of the mechanisms for resistance anticancer drugs, we found that the resistance is associated with the P-glycoprotein which is encoded by Multi-drug resistance gene1. P-gp is the archetypal example of multidrug transport proteins.Which can pump drugs that entered into the brain and neurons,and regulation of intracellular drug content. So, some rensons that made P-gp over expression on the blood-brain barrier may limit AEDs penetration into the brain,which leading to the occurrence of resistance. In2003, Siddiqui et al. firstly reported the C3435T polymorphism in the MDR1gene as being associated with resistance to AEDs,the Single Nucleotide Polymorphism cound increased the expression of P-gp and enhanced its function, thereby reduced the level of AED distributed in the brain. Since this study thought that drug resistance in epilepsy might be genetically determined for the first time, many scholars have conducted a lot of research of it. while, the result is quite different, Some studies have even come to the opposite conclusions.Taking into account the above findings may be related to racial differences in regional disparities, this study will analysis the relationship between two single nucleotide polymorphisms of multidrug resistance gene1and Henan Han children with refractory epilepsy, and detect their mechanisms of molecular genetics.MethodsDNA samples were obtained from Henan Provincial People’s Hospital, A total of260cases were enrolled, including60cases of refractory epilepsy,100cases of drug-responsive epilepsy and100cases of healthy children. The genotypes and allele frequencies for MDR1polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. SPSS17.0software was applied for statistical treatment. P<0.05was considered statistically significant.ResultsC3435T:The genotype of refractory epilepsy group was given priority to with TC, the frequency distribution has no correlation between it and drug responsive group,but significantly higher than healthy control group, and the difference was statistically significant (P=0.031), but there was no statistical difference between the two alleles.T129C:The drug-responsive group and healthy control group have the same number of genotypes, the CC genotype was not found in all of the three groups.The distribution of TC genotype and T allele frequencies of refractory epilepsy group differed significantly from that in drug-responsive group and healthy control group (P=0.029,0.034).ConclusionC3435T and T129C polymorphisms of the MDR1gene were associated with refractory epilepsy in Chinese Henan Han children and may play some role in the cause of resistance mechanisms for refractory epilepsy. |
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