基于倾向性评分匹配探讨载脂蛋白E水平及其基因多态性与脑血栓形成的相关性分析

Correlation between ApoE level and its gene polymorphism and cerebral thrombosis based on propensity score matching

目的基于倾向性评分匹配(PSM)探讨载脂蛋白(Apo)E水平及其基因多态性与脑血栓形成的相关性。方法选取2019年12月至2021年1月在南方医科大学附属佛山医院神经内科门诊拟诊为早期脑血栓形成的患者,对其进行评估并随访6个月,根据随访期间再次就诊的临床症状及影像学诊断结果,将疑似患者(312例)分为脑血栓组(144例)和对照组(168例)。采用PSM设计,按1∶1最邻近方法进行匹配,有效平衡甘油三酯、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、ApoA、ApoB、D-二聚体、纤维蛋白原、空腹葡萄糖等与脑血栓形成相关危险因素后,近似匹配成功87对。分析比较两组患者ApoE基因型、携带基因频率及不同ApoE基因型与ApoE水平的关系。结果脑血栓组携带ε4基因频率(57.47%)明显高于对照组(24.14%),携带ε2基因频率(17.24%)明显低于对照组(42.53%),差异均有统计学意义(P<0.05);脑血栓组携带ε3基因频率(77.01%)与对照组(83.91%)比较,差异无统计学意义(P>0.05)。不同ApoE基因型脑血栓组对应的血清ApoE水平均明显高于对照组,差异均有统计学意义(P<0.05)。无论是脑血栓组还是对照组,携带一个或超过一个ε4基因型时,其对应的血清ApoE水平均明显高于其他基因型,差异均有统计学意义(P<0.05)。结论血清高水平ApoE可能是脑血栓形成的独立危险因素,且ε4基因型是ApoE的高危基因型,其对应的血清ApoE水平明显升高。ApoE水平及其基因型可作为监测及早期评估脑血栓形成风险的新标志物。

Objective To investigate the correlation between apolipoprotein(Apo)E level and its gene polymorphism and cerebral thrombosis based on propensity score matching(PSM).Methods Patients who were suspected of early cerebral thrombosis in the outpatient Department of Neurology of Foshan Hospital Affiliated to Southern Medical University from December 2019 to January 2021 were selected for evaluation and followed up for 6 months.According to the clinical symptoms and imaging diagnosis results of re-visits during the follow-up period,suspected patients(312 cases)were divided into cerebral thrombosis group(144 cases)and control group(168 cases).PSM design was adopted and matched according to the 1∶1 nearest neighbor method.After effectively balancing triglyceride,total cholesterol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,ApoA,ApoB,D-dimer,fibrinogen,fasting glucose and other risk factors related to cerebral thrombosis,87 pairs were approximately matched successfully.ApoE genotypes,allele frequencies and the relationship between different ApoE genotypes and ApoE levels were compared between the two groups.Results The frequency ofε4 gene in cerebral thrombosis group(57.47%)was significantly higher than that in control group(24.14%),and the frequency ofε2 gene in cerebral thrombosis group(17.24%)was significantly lower than that in control group(42.53%),the differences were statistically significant(P<0.05).There was no significant difference in the frequency of carrying theε3 gene between the cerebral thrombosis group(77.01%)and the control group(83.91%)(P>0.05).Serum ApoE levels in cerebral thrombosis group with different ApoE genotypes were significantly higher than those in the control group with the same genotypes,the differences were statistically significant(P<0.05).Whether in the cerebral thrombosis group or the control group,when one or more than oneε4 gene were carried,the corresponding serum ApoE levels were significantly higher than those of other genotypes,the differences were statistically significant(P<0.05).Conclusion High serum level of ApoE may be an independent risk factor for cerebral thrombosis,and theε4 gene is the high-risk genotype of ApoE,and its corresponding serum ApoE level significantly increases.ApoE level and its genotype could be used as a new marker to monitor and evaluate early the formation of cerebral thrombosis.