CLU基因多态性与缺血性脑卒中后癫痫风险的关系分析

Relationship between CLU gene polymorphisms and post-ischemic stroke epilepsy

目的:探讨聚集素蛋白(CLU)基因单核苷酸多态性(SNPs)与缺血性脑卒中后癫痫的遗传学关系。方法:2017年1月至2021年8月,共纳入249例缺血性脑卒中后癫痫患者(癫痫组)和250例没有继发性癫痫的缺血性脑卒中患者(对照组)。选取3个CLU单核苷酸多态性(rs11136000、rs9314349和rs9331949),通过SNaPshot检测进行基因分型,并评估它们与缺血性脑卒中后癫痫的关系。采用酶联免疫吸附测定法检测脑卒中发病入院时的血清CLU水平。结果:癫痫组与对照组rs11136000位点基因型和等位基因分布频率差异有统计学意义(P<0.05),但是rs9314349位点和rs9331949位点基因型分布及等位基因频率差异均无统计学意义(P>0.05)。与TT基因型相比,CC基因型和TC基因型与脑卒中后癫痫风险降低相关(P<0.05)。女性和男性CLU rs11136000位点TC/CC基因型频率降低与脑卒中后癫痫的关系显著(P<0.01)。经多因素Logistic回归分析,CLU基因rs11136000位点TC和CC基因型都是脑卒中后癫痫发病风险的独立保护因素(P<0.05)。癫痫组患者血清CLU水平显著低于对照组[73.10(57.70,100.50)μg·ml^(-1) vs.66.86(54.60,82.60)μg·ml^(-1),Z=-3.619,P<0.001]。在癫痫组中,CLU基因rs11136000位点TC/CC基因型患者(C等位基因携带者)血清CLU水平显著高于TT基因型患者(P<0.05)。结论:CLU基因rs11136000位点TC/CC基因型分布频率降低与缺血性脑卒中后癫痫易感性升高有关。

Objective:To investigate the genetic relationship between the Clusterin(CLU)gene single-nucleotide polymorphisms(SNPs)and post-ischemic stroke epilepsy.Methods:From January 2017 to August 2021,a total of 249 patients with post-ischemic stroke epilepsy(epilepsy group)and 250 ischemic stroke patients without secondary epilepsy(control group)were included.Three sites SNPs of CLU(rs11136000,rs9314349 and rs9331949)were selected for genotyping by SNaPshot test and their association with post-ischemic stroke epilepsy was evaluated.The level of serum CLU was measured by enzyme-linked immunosorbent assay when ischemic stroke patients were admitted to hospital.Results:The genotype and allele frequencies of rs11136000 locus in epilepsy group and control group were significantly different(P<0.05),but the genotype and allele frequencies of rs9314349 locus and rs9331949 locus were not significantly different(P>0.05).Compared with TT genotype,CC and TC genotype were associated with a lower risk of epilepsy after stroke(P<0.05).The decrease of TC/CC genotype frequency at rs11136000 locus of CLU gene in women and men was significantly associated with post-stroke epilepsy(P<0.01).By multivariate Logistic regression analysis,TC and CC genotypes at rs11136000 of CLU gene were independent protective factors for the risk of epilepsy after stroke(P<0.05).Serum CLU level in epilepsy group was significantly lower than that in control group[73.10(57.70,100.50)μg·ml^(-1) vs.66.86(54.60,82.60)μg·ml^(-1),Z=-3.619,P<0.001].In the epilepsy group,the level of serum CLU in the rs11136000 TC/CC genotype(C allele carrier)was significantly higher than that in the TT genotype(P<0.05).Conclusion:The decrease of the frequency of TC/CC genotype at rs11136000 site of CLU gene is associated with the increased susceptibility to post-ischemic stroke epilepsy.