BACKGROUND:There are two hypotheses for the underlying cause of refractory epilepsy:“target”and“transport”.Studies have shown that brain-derived neurotrophic factor(BDNF) is over-expressed in refractory epilepsy.Multidrug resistance 1(MDR1) gene encodes for P-glycoprotein,the primary ATP-binding cassette transporter in the human body.Some single nucleotide polymorphisms of the MDR1 gene have been associated with refractory epilepsy. OBJECTIVE:To investigate the association between BDNF gene C270T polymorphism and MDR1 T-129C polymorphism with refractory epilepsy in Chinese Han children through the use of polymerase chain reaction(PCR)-restriction fragment length polymorphism analysis. DESIGN,TIME AND SETTING:A case-control,genetic association study was performed at the Central Laboratory,Third Xiangya Hospital of Central South University from June 2005 to November 2007. PARTICIPANTS:A total of 84 cases of unrelated children with epilepsy,including 41 cases of refractory epilepsy and 43 cases of drug-responsive epilepsy,were enrolled.An additional 30 healthy,Chinese Han children,whose ages and gender matched the refractory epilepsy patients, were selected as normal controls. METHODS:Venous blood was collected and genomic DNA was extracted from the blood specimens.C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene were genotyped using PCR-restriction fragment length polymorphism analysis.Association analysis using the Ftest and Chi-square test was statistically performed between C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene and refractory epilepsy. MAIN OUTCOME MEASURES:The distribution of genotypes and allele frequencies of C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene. RESULTS:The distribution of CC,CT,and TT genotypes,as well as C and T allele frequencies,in the BDNF gene was not significantly different between the refractory epilepsy group, drug-responsive epilepsy group,or the normal control group(P>0.05).The distribution of TT genotype and T allele frequencies of the MDR1 gene was significantly different in the refractory epilepsy group compared with the drug-responsive epilepsy and normal control groups(P<0.05). Comparison of haplotype combinations demonstrated that there were no significant differences in combinations of TT+CC,TT+CT,TC+CC,and TC+CT among the three groups(P>0.05). CONCLUSION:C270T polymorphism of the BDNF gene was not associated with refractory epilepsy in Chinese Han children,but T-129C polymorphism in the MDR1 gene was associated with refractory epilepsy in Chinese Han children.The TT genotype and T allele frequencies could serve as susceptibility loci for refractory epilepsy.Interactions between C270T in BDNF gene and T-129C in MDR1 gene were not observed in refractory epilepsy in Chinese Han children. BACKGROUND: There are two hypotheses for the underlying cause of refractory epilepsy: “target ” and “transport ”. Studies have shown that brain-derived neurotrophic factor (BDNF) is over-expressed in refractory epilepsy. Multidrug resistance 1 ( MDR1) gene encodes for P-glycoprotein, the primary ATP-binding cassette transporter in the human body. Single single nucleotide polymorphisms of the MDR1 gene have been associated with refractory epilepsy. OBJECTIVE: To investigate the association between BDNF gene C270T polymorphism and MDR1 T -129C polymorphism with refractory epilepsy in Chinese Han children through the use of polymerase chain reaction (PCR) -restriction fragment length polymorphism analysis. DESIGN, TIME AND SETTING: A case-control, genetic association study was performed at the Central Laboratory, Third Xiangya Hospital of Central South University from June 2005 to November 2007. PARTICIPANTS: A total of 84 cases of unrelated children with epilepsy, including 41 cases of refractory epilepsy an d 43 cases of drug-responsive epilepsy, were enrolled. An additional 30 healthy, Chinese Han children, whose ages and gender matched the refractory epilepsy patients, were selected as normal controls. METHODS: Venous blood was collected and genomic DNA was extracted from the blood specimens. C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene were genotyped using PCR-restriction fragment length polymorphism analysis. Association analysis using the Ftest and Chi-square test was performed between C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene and refractory epilepsy. MAIN OUTCOME MEASURES: The distribution of genotypes and allele frequencies of C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene. RESULTS: The distribution of CC, CT, and TT genotypes, as well as C and T allele frequencies, in the BDNF gene was not significantly different between the refractory epilepsy group, drug-responsive epilepsy group, or the normal control grouThe distribution of TT genotype and T allele frequencies of the MDR1 gene was significantly different in the refractory epilepsy group compared with the drug-responsive epilepsy and normal control groups (P <0.05). that there was no significant differences in combinations of TT + CC, TT + CT, TC + CC, and TC + CT among the three groups (P> 0.05). CONCLUSION: C270T polymorphism of the BDNF gene was not associated with refractory epilepsy in Chinese Han children, but T-129C polymorphism in the MDR1 gene was associated with refractory epilepsy in Chinese Han children. The TT genotype and T allele frequencies could serve as susceptibility loci for refractory epilepsy. Betweenteractions between C270T in BDNF gene and T-129C in MDR1 gene were not observed in refractory epilepsy in Chinese Han children.