Frequency Of The C1236T Polymorphism In MDR1 Genes And Association Of This Polymorphisms With Multidrug-resistant Epilepsy

BackgroundEpilepsy is one of the most common neurological disorders,although the prognosis for the majority of patients is good,up to 30%of patiens continue to have seizures despite carefully optimized antiepileptic drug treatment.Many researches suggest that this phenomenon is associated with multiple drug resistance 1(MDR1) gene.Recent years,Single Nucleotide Polymorphism(SNP)of gene has been generally used in genetics.It is suggest that the SNP relate to the expression and function of MDR1 gene and p-glycoprotein encoded by MDR1 gene.To study the SNP in MDR1 gene conduce to interpret the difference of individual phenotype and explain the affectability of different reactivity to antiepileptic drug treatment.The SNP at the C1236T in exon 12 is one of the most popular locus.It is located in non-coding regions and does not lead to a change in the amino acid sequence.It has suggested that C1236T is related to drug resistance in several diseases.ObjectiveTo determine the frequency of polymorphism at C1236T of MDR1 in epileptic patients and study the association of this polymorphism with antiepileptic drug treatment in epileptic patients.Futher more,to determine the frequency of polymorphism at C1236T of MDR1 gene in epileptic patients with different seizures and different causes to diseases and study the association of this polymorphism with antiepileptic drug treatment in these patients.MethodsDNA samples were obtained from Qilu Hospital of Shandong University and Zibo city Changguo Hospital of Red Cross Association,of whom 70 were resistant to antiepileptic drug treatment and 88 were responsive to the treatment.Genotypes of the C1236T polymorphism were determined by polymerase chain reaction(PCR)followed by restrictionfragment length polymorphism(RFLP).Genotype and allele frequencies in the drug resistant group were compared with those in the response group by Chi-square analysis.Correction for genetic stratification was undertaken with use of the spss 13.0 software.All reported P values are two-sided,a P value of less than 0.05 was considered to indicate statistical significance.Results1,Of all 158 patients,30 had CC genotype,49 had CT genotype,and 79 had TT genotype.The pharmacoresistance group contain 70 patients,16 had CC genotype, 19 had CT genotype,and 35 had TT genotype.The responsive group contain 88 patients,14 had CC genotype,30 had CT genotype,and 44 had TT genotype.The frequency of CC genotype was significantly higher in the pharmacoresistance group than that in the responsive group.The frequency of TT genotype was equality in two groups.The frequency of CT genotype was significantly lower in the pharmacoresistance group.The frequency of the C allele was higher in the pharmacoresistance group than that in the responsive group.But there were no significant differences both in the genotype frequency and allele frequency between the two groups.2,All 158 patients was divided to two groups according to ages.(1)The groups of whom was less than 13 years old has 45 patients.Genotype and allele frequencies in the drug resistant group were compared with those in the response group by Chi-square analysis.There was no significant diference(P＞0.05).(2)Of all 133 more than 13 years old patients,no significant diference was found beween the frequency of genotype and allele frequencies either,P＞0.05.3,All epileptic patients were divided into 3 parts by types of seizures according to clinical data and electrocardiogram(EEG) examination.(1)46 patients with partial seizures,the samples were too little to analyze the genotype frequency.To evaluate the diference of C and T between two groups,there were significant diference P=0.038.(2)35 patients with generalized seizures,there were no significant differences both in the genotype frequency and allele frequency between the two groups(P＞0.05).(3)Of all 67 patients,there were no significant differences both in the genotype frequency and allele frequency between the two groups(P＞0.05).4,All patients were divided by etiologic into symptomatic epilepsy group and idiopathic epilepsy group or cryprogenic epilepsy group according to clinical data,EEG examination and image examination.(1)In all 56 symptomatic epilepstic patients,to evaluate the diference of genotype and allele frequency between two groups,there were significant diference(P＞0.05).(2)Of all 94 idiopathic epilepsy group or cryprogenic epileptic patients,there were no significant differences both in the genotype frequency and allele frequency between the two groups(P＞0.05).Conclusions1,There is no association between at the locus of C1236T in MDRI gene and response to antiepileptic drug treatment in Chinese patients with epilepsy.2,All patients were divided to two groups by ages..There were no significant differences of the genotype and allele frequency in two groups.It suggests that age is not the reason of distributional difference of SNP at C1236T in MDR1 gene.3,Patients were divided to three groups by types of seizures.C allele frequency was higher in pharmacoresistance of the partial seizure group.It suggests that C allele frequency maybe the risk factors of pharmacoresistance.It could explain patients with partial seizure are more common to resistant to antiepileptic drug treatment.4,Patients were divided to two groups by etiologic.To evaluate the diference of genotype and allele frequency between two groups respectively.The result suggests that there is no association between C1236T in MDRI gene and response to antiepileptic drug treatment in Chinese patients with different etiological epilepsy.