载脂蛋白E基因单核苷酸多态性与癫痫耐药的相关性研究

Association between single nucleotide polymorphisms of apolipoprotein E gene and drug resistance in epilepsy

目的探讨汉族人群中载脂蛋白E（apolipoprotein E,Apo E）基因2个单核苷酸多态（single nucleotidepolymorphism,SNPs）位点与癫痫耐药的相关性。方法选取2011年5月-2014年5月期间于我院神经内科癫痫专科门诊患者317例,其中耐药性癫痫患者（耐药组）142例,非耐药性癫痫患者（非耐药组）175例。对入组患者抽取外周静脉血并提取全基因组DNA,对Apo E基因的rs7412与rs769450位点进行基因分型,比较癫痫耐药组与非耐药组患者等位基因频率、基因型频率及位点间连锁不平衡差异。结果与非耐药组比较,耐药组rs769450位点GG基因型（OR=2.041,95%CI 1.195~3.457,P=0.010）和G等位基因（1.619,95%CI 1.191~2.196,P=0.002）的频率较高;两组的rs7412位点在基因型和等位基因频率分布上无明显差异;耐药组rs769450位点GG基因型（OR=2.041,95%CI 1.196~3.557,P=0.011）和G等位基因（OR=1.639,95%CI 1.181~2.185）,P=0.003）较高,差异具有统计学意义。通过SHEsis平台对两位点进行连锁不平衡分析,提示rs7412和rs769450位点间不存在连锁不平衡（D’=0.073）。结论 Apo E rs769450 GG基因型及G等位基因在汉族人群中可能与癫痫耐药相关。

Objective To investigate the possible association between two single nucleotide polymorphisms（ SNPs）loci of apolipoprotein E（ Apo E） gene and epileptic drug resistance in Chinese Han population. Method Four hundred and fifty-nine cases of patients with epilepsy in our hospital from May 2011 to May 2014 was assigned into the drug resistant group（ n = 142 cases） and the drug responsive group（ n = 175 cases）. The peripheral venous blood of patients was collected for DNA extraction after clinical evaluation. Genotyping of rs7412 and rs769450 loci of Apo E gene was performed to compare the differences of allele frequency,genotype frequency and linkage disequilibrium between the two groups. Result Compared with the drug responsive group,the rs769450 GG genotype（ OR = 2. 041,95% CI 1. 195 ~ 3. 457,P = 0. 010） and G allele（ 1. 619,95% CI 1. 191 ~ 2. 196,P = 0. 002） in the drug resistant group had high frequency; the rs7412 loci of the genotype and allele frequency distribution in the two groups had no obvious difference; as for idiopathic epileptic patients,the GG gene type（ OR = 2. 041,95% CI 1. 196 - 3. 557,P = 0. 011） and G allele（ OR = 1. 639,95% CI 1. 181 - 2. 185,P= 0. 003） of rs769450 in the resistance group had high frequency. The linkage disequilibrium analysis indicated that there was no linkage disequilibrium between rs7412 and rs769450（ D＇= 0. 073）. Conclusion GG and G allele of Apo E Rs769450 may be associated with drug resistance in the Han population.