CLU基因多态性与缺血性脑卒中后癫痫风险的关系分析-东南大学学报医学版

CLU基因多态性与缺血性脑卒中后癫痫风险的关系分析

单位：1. 万宁市人民医院神经内科, 海南万宁 571500;
2. 海南医学院第二附属医院神经内科, 海南海口 570216

分类号：R742.1;R743.3;R969

出版年·卷·期（页码）：2022·41·第四期（491-497）

摘要：

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.

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