淀粉蛋白前β位分解酶1基因多态性与癫痫易感性的关系

Relationship between BACE1 gene polymorphisms and epilepsy susceptibility

目的分析淀粉蛋白前β位分解酶1(BACE1)基因多态性与癫痫易感性的关系。方法选取湖南地区238例癫痫患者为观察组(男129例,女109例)、体检健康者211例为对照组(男104例,女107例),均为汉族,采用PCR-连接酶检测反应(LDR)检测BACE1基因rs535860、rs525493、rs638405位点的多态性,分析其与癫痫发病的关系。结果观察组BACE1基因rs535860基因型AT频率高于对照组(P=0.041),携带至少1个突变等位基因T(AT+TT)的个体癫痫发病风险是野生AA基因型的1.005倍(95%CI:0.382~2.616,P=0.048);两组BACE1基因rs525493、rs638405的基因型和等位基因分布差异无统计学意义(P均>0.05)。观察组男性癫痫患者BACE1基因s535860基因型AT频率高于对照组男性人群(P=0.004),携带至少1个突变等位基因T(AT+TT)的男性个体癫痫发病风险是野生AA基因型的2.585倍(95%CI:1.310~5.140,P=0.006)。两组男性人群BACE1基因rs525493、rs638405及女性人群rs535860、rs525493、rs638405的基因型和等位基因分布差异无统计学意义(P均>0.05)。结论 BACE1基因rs535860突变杂合子AT基因型与癫痫的发病有关,在男性群体中更为显著。

Objective To analyze the relationship between the β-secretase 1（ BACE1） gene polymorphisms and epilepsy susceptibility. Methods BACE1 gene rs535860,rs525493 and rs638405 polymorphisms were detected by the PCRligase detection reaction（ LDR） in 238 children with epilepsy（ observation group,129 males and 109 females） and 211 healthy controls（ control group,104 males and 107 females） of Han population in Hunan Province,and their correlations with epilepsy susceptibility was analyzed. Results The frequency of genotype AT for BACE1 rs535860（ A T） was significantly higher in the observation group than in the control group（ P = 0. 041）. The incidence rate of patients that carried the T allele（ AT ＋ TT） was 1. 005 times higher than that carried AA wild genotype（ 95% CI 0. 382-2. 616,P = 0. 048）.However,no statistically significant differences were found in the genotype and allele distributions of rs525493（ G T） and rs638405（ C G） between the two groups（ all P〈0. 05）. The genotype AT frequency of BACE1 gene s535860 in male patients with epilepsy of the observation group was higher than that in the control group（ P = 0. 004）. The risk of epilepsy in male individuals carrying at least one mutant allele T（ AT ＋ TT） was 2. 585 times higher than that of males with wild AA genotype（ 95% CI： 1. 310-5. 140,P = 0. 006）. There was no significant difference in genotype and allele distribution of BACE1 gene rs525493,rs638405 of males as well as BACE1 gene rs535860,rs525493 and rs638405 of females between these two groups（ all P〈0. 05）. Conclusion The mutant heterozygote AT genotype of BACE1 gene rs535860 is associated with the onset of epilepsy and is more significant in males.