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中华脑科疾病与康复杂志(电子版) ›› 2025, Vol. 15 ›› Issue (04) : 220 -226. doi: 10.3877/cma.j.issn.2095-123X.2025.04.005

临床研究

载脂蛋白E基因多态性对急性缺血性脑卒中后抑郁的影响
刘佳成1, 许晓辉2, 杜艳姣2, 张云亭1, 段智慧2,†()   
  1. 1453003　河南新乡，新乡医学院
    2471000　河南洛阳，洛阳市中心医院神经内科
  • 收稿日期:2024-12-30 出版日期:2025-08-15
  • 通信作者: 段智慧

Effect of apolipoprotein E gene polymorphisms on post-stroke depression after acute ischemic stroke

Jiacheng Liu1, Xiaohui Xu2, Yanjiao Du2, Yunting Zhang1, Zhihui Duan2,†()   

  1. 1Xinxiang Medical University, Xinxiang 453003, China
    2Department of Neurology, Luoyang Central Hospital, Luoyang 471000, China
  • Received:2024-12-30 Published:2025-08-15
  • Corresponding author: Zhihui Duan
  • Supported by:
    Science and Technology Development Program of Henan Province in 2023(232102310101)
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引用本文：

刘佳成, 许晓辉, 杜艳姣, 张云亭, 段智慧. 载脂蛋白E基因多态性对急性缺血性脑卒中后抑郁的影响[J/OL]. 中华脑科疾病与康复杂志(电子版), 2025, 15(04): 220-226.

Jiacheng Liu, Xiaohui Xu, Yanjiao Du, Yunting Zhang, Zhihui Duan. Effect of apolipoprotein E gene polymorphisms on post-stroke depression after acute ischemic stroke[J/OL]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2025, 15(04): 220-226.

目的

探讨载脂蛋白E（APOE）基因多态性对急性缺血性脑卒中后抑郁（PSD）的影响。

方法

连续性纳入洛阳市中心医院神经内科自2024年1月1日至12月1日收治的180例急性缺血性脑卒中患者，入院24 h内进行常规血液学检查，采用美国国立卫生研究院卒中量表（NIHSS）评估患者的神经功能缺损程度，改良Rankin量表（mRS）评估患者的残障程度。在卒中发病后的2、3周和1个月采用汉密尔顿抑郁量表（HAMD）评估患者的抑郁情况。根据是否合并有PSD将患者分为PSD组和非PSD（NPSD）组，采用实时荧光定量PCR检测2组患者APOE基因多态性。比较2组患者的基线临床资料、实验室检查结果、APOE基因型分布、等位基因频率。采用多因素Logistic回归法分析PSD的影响因素。

结果

PSD组患者62例，NPSD组患者118例。2组患者的基线临床资料比较，差异均无统计学差异（P>0.05）。PSD组患者血清总胆固醇（CHOL）、同型半胱氨酸（HCY）水平高于NPSD组，叶酸水平低于NPSD组，差异均有统计学意义（P<0.05）。PSD组患者ε3ε4、ε4ε4基因型分布频率高于NPSD组，ε2等位基因频率低于NPSD组，ε4等位基因频率高于NPSD组，差异均有统计学意义（P<0.05）。PSD组中携带ε4等位基因的患者HAMD评分高于未携带ε4等位基因的患者，差异有统计学意义（P<0.05）。所有携带ε4等位基因的患者NIHSS、mRS评分高于未携带者，差异均有统计学意义（P<0.05）。多因素Logistic回归分析显示，血清CHOL、HCY水平及ε4等位基因是PSD发病的独立危险因素（P<0.05）。

结论

APOE基因多态性与PSD有关，ε4等位基因是PSD发病的独立危险因素，血清CHOL及HCY水平升高可能会增加PSD的发病风险。

关键词: 急性缺血性脑卒中, 卒中后抑郁, 载脂蛋白E, 基因多态性, ε4等位基因
Objective

To investigate the effect of apolipoprotein E (APOE) gene polymorphisms on post-stroke depression (PSD) after acute ischemic stroke.

Methods

A total of 180 patients with acute ischemic stroke admitted to the Department of Neurology of Luoyang Central Hospital from January 1 to December 1, 2024 were continuously included. Routine hematological examinations were conducted within 24 h of admission, and the National Institutes of Health stroke scale (NIHSS) score was used to assess the degree of neurological deficits in stroke patients, while the modified Rankin scale (mRS) score was used to assess the degree of disability in stroke patients. The Hamilton depression scale (HAMD) was used to assess the depression status of patients at 2, 3 weeks, and 1 month after the onset of stroke. Patients were divided into PSD group and non PSD (NPSD) group based on whether PSD was present. Real-time fluorescence quantitative PCR was used to detect APOE gene polymorphisms in the 2 groups, and baseline clinical data, laboratory tests, APOE genotype distribution, and allele frequency were compared between the 2 groups. Multiple Logistic regression was used to analyze the influencing factors of PSD.

Results

There were 62 patients in the PSD group and 118 patients in the NPSD group. There was no statistically significant difference in the general clinical data between the two groups (P>0.05). The serum total cholesterol (CHOL) and homocysteine (HCY) levels of patients in PSD group were higher than those in NPSD group, and the folic acid levels were lower than those in NPSD group, and the differences were statistically significant (P<0.05). The distribution frequency of the ε3ε4 and ε4ε4 genotypes in PSD group patients was higher than that in NPSD group, the frequency of the ε2 allele was lower than that in NPSD group, and the frequency of the ε4 allele was higher than that in NPSD group, the differences were statistically significant (P<0.05). The HAMD scores of patients carrying the ε4 allele were higher than those of patients without the ε4 allele in the PSD group, and the difference was statistically significant (P<0.05). All patients carrying the ε4 allele had higher NIHSS and mRS scores than those without the allele, and the differences were statistically significant (P<0.05). Multiple Logistic regression analysis showed that serum CHOL and HCY levels, and the ε4 allele, were independent risk factors for the development of PSD (P<0.05).

Conclusions

The polymorphism of APOE gene is closely related to PSD, and the ε4 allele is an independent risk factor influencing the development of PSD. Elevated serum CHOL and HCY levels may increase the risk of developing PSD.

Key words: Acute ischemic stroke, Post-stroke depression, Apolipoprotein E, Gene polymorphism, ε4 allele
表1 2组急性缺血性脑卒中患者的临床资料比较
Tab.1 Comparison of clinical data between 2 groups of acute ischemic stroke patients
项目 PSD组（n=62） NPSD组（n=118） χ2/Z值 P值
年龄[岁，M（P25，P75）] 61.5（51，74） 61.5（50.75，71.25） -0.205 0.838
性别[例（%）]     0.014 0.906
男 30（48.39） 62（52.54）    
女 32（51.61） 56（47.46）    
高血压病[例（%）] 41（66.13） 79（66.95） 0.012 0.912
糖尿病[例（%）] 16（25.81） 32（27.12） 0.036 0.850
冠心病[例（%）] 7（11.29） 12（10.17） 0.054 0.816
脑卒中史[例（%）] 19（30.65） 43（36.44） 0.605 0.437
吸烟史[例（%）] 24（38.71） 51（43.22） 0.340 0.560
饮酒史[例（%）] 3（4.84） 7（5.93） 0.001 0.970
GLU[mmol/L，M（P25，P75）] 5.85（5.18，7.34） 5.65（5.08，6.53） -0.241 0.810
TG[mmol/L，M（P25，P75）] 1.40（1.01，2.21） 1.50（0.98，2.01） -1.167 0.243
LDL-C[mmol/L，M（P25，P75）] 2.48（2.02，3.25） 2.65（1.93，3.20） -0.059 0.953
HDL-C[mmol/L，M（P25，P75）] 0.91（0.79，1.26） 0.96（0.77，1.32） -0.425 0.671
T3[pmol/L，M（P25，P75）] 4.82（4.11，5.52） 5.07（4.42，5.58） -1.544 0.122
T4[pmol/L，M（P25，P75）] 15.75（14.33，17.28） 15.91（14.49，17.23） -0.056 0.956
TSH[μU/mL，M（P25，P75）] 1.97（1.30，2.91） 2.16（1.49，2.80） -0.774 0.439
CHOL[mmol/L，M（P25，P75）] 4.57（3.75，5.23） 4.02（3.47，4.62） -3.442 0.001
HCY[μmol/L，M（P25，P75）] 19.66（15.99，25.37） 14.90（12.33，21.08） -4.910 <0.001
FOL[ng/mL，M（P25，P75）] 7.5（4.51，11.62） 8.95（4.85，15.87） -2.450 0.014
NIHSS评分[分，M（P25，P75）] 11（9，12） 10（8，12） -1.210 0.226
mRS评分[分，M（P25，P75）] 3（2，3） 2（2，3） -2.750 0.006
APOE等位基因[频数（%）]        
ε2 9（7.26） 36（15.25） 4.752 0.030
ε3 83（66.94） 171（72.46） 1.193 0.274
ε4 32（25.81） 29（12.29） 10.556 0.001
表2 脑卒中后抑郁影响因素的多因素Logistic回归分析
Tab.2 Multifactorial Logistic regression analysis of factors influencing post-stroke depression
因素 偏回归系数 标准误 Walds值 OR值 95%CI P值
CHOL 0.905 0.255 12.611 2.471 1.500~4.071 <0.001
FOL -0.062 0.038 2.615 0.940 0.872~1.013 0.106
HCY 0.149 0.041 13.100 1.161 1.071~1.258 <0.001
mRS -0.195 0.311 0.393 0.823 0.447~1.513 0.531
ε2 0.122 0.534 0.052 1.130 0.397~3.221 0.819
ε4 0.969 0.482 4.038 2.636 1.024~6.782 0.044
常量 -6.463 1.602 16.265 0.002   <0.001
表3 2组急性缺血性脑卒中患者APOE基因型分布情况比较[例（%）]
Tab.3 Comparison of APOE genotype distribution between 2 groups of acute ischemic stroke patients [n（%）]
组别 例数 ε2ε2 ε2ε3 ε2ε4 ε3ε3 ε3ε4 ε4ε4
PSD组 62 1（1.61） 5（8.06） 2（3.23） 29（46.77） 20（32.26） 5（8.06）
NPSD组 118 6（5.08） 15（12.71） 9（7.63） 70（59.32） 16（13.56） 2（1.69）
χ2值   1.311 0.889 1.372 2.586 8.882 4.412
P值   0.252 0.346 0.241 0.108 0.003 0.036
表4 PSD组不同APOE等位基因携带者HAMD评分情况比较[分，M（P25，P75）]
Tab.4 Comparison of HAMD scores among carriers of different alleles in the PSD group [score, M（P25，P75）]
等位基因 例数 HAMD评分
ε2 8 12（10，13.75）
ε3 54 13（12，15）
ε4 27 15（13，16）ab
χ2值   11.129
P值   0.004
表5 不同等位基因携带者NIHSS与mRS评分情况比较[分，M（P25，P75）]
Tab.5 Comparison of NIHSS and mRS scores in carriers of different alleles [score, M（P25，P75）]
等位基因 例数 NIHSS评分 mRS评分
ε2 38 9（8，11） 2（2，3）
ε3 155 10（9，12）a 3（2，3）a
ε4 54 11（9.75，12）ab 4（3，4）ab
χ2值   20.031 56.955
P值   <0.001 <0.001
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