Association of single nucleotide polymorphisms of brain-derived neurotrophic factor gene and multidrug resistance 1 gene to refractory epilepsy in Chinese Han children

摘要

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(P0.05). 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.