Expression of multidrug resistance 1 gene and C3435T genetic polymorphism in peripheral blood of patients with intractable epilepsy

摘要

BACKGROUND:Increased expression of multidrug resistance 1 (MDR1) mRNA in peripheral blood of pa-tients with intractable epilepsy is not due to epilepsy drugs,but epilepsy behavior. Monitoring MDR1 ex-pression in peripheral blood is a target for MDR1 gene evaluation. OBJECTIVE: To investigate the influence of antiepileptic drugs and seizures on MDR expression in intrac-table epilepsy,and to analyze the genetic polymorphisms of C3435T in the MDR1 gene. DESIGN,TIME AND SETTING: Factorial designs and comparative observations at the experimental cen-ter of the Affiliated Hospital of Qingdao Medical College,Qingdao University between October 2003 and October 2004. PARTICIPANTS: A total of 120 subjects were recruited from the epilepsy clinical department of the Affili-ated Hospital of Qingdao Medical College. Four groups (n=30) were classified according to statistical fac-torial design: intractable epilepsy,treatment response,no treatment,and normal control groups. METHODS: One-step semi-quantitative reverse-transcription polymerase chain reaction technology was used to test expressions of the MDR1 gene in 120 subjects. C3435T polymorphisms in intractable epilepsy group and normal control groups were analyzed by polymerase chain reaction-restriction fragment length polymorphism. MAIN OUTCOME MEASURES: Expression of MDR1 mRNA in the four groups,and C3435T genetic polymorphisms in intractable epilepsy and normal control groups. RESULTS: MDR1 gene expression was increased in the intractable epilepsy group,due to the factor sei-zures,but not the antiepileptic drugs. However,the interaction between the two factors was not statistically significant. Of the 30 subjects in the intractable epilepsy group,the following genotypes were exhibited: 3 (10%) C/C genotype,9 (30%) C/T genotype,and 18 (60%) T/T genotype at the site of C3435T,while 4 (13%),10 (33%),and 16 (53%) subjects were determined to express these genotypes in the normal control group,respectively. C and T allele frequency were 25% and 75% in the intractable epilepsy group,and 30% and 70% in the normal control group,respectively. However,there was no statistical difference between the groups. CONCLUSION: Results demonstrated that seizures,not antiepileptic drugs,induced MDR1 gene expres-sion in intractable epilepsy. Genetic polymorphisms of C3435T in the MDR1 gene did not contribute to the development of multidrug resistance in patients with intractable epilepsy.