中国临床神经外科杂志

目的 探讨载脂蛋白E(ApoE)基因多态性与阿托伐他汀治疗亚急性硬脑膜下血肿（SSDH）钻孔引流术后残余血肿疗效的相关性，为个体化治疗提供遗传学依据。方法 回顾性分析2020年1月至2024年6月佛山市第一人民医院神经外科收治的152例接受钻孔引流术并规律服用阿托伐他汀（20 mg/d，≥4周）且有ApoE基因型检测结果的SSDH患者临床资料。采用PCR-RFLP法进行ApoE基因分型，使用3D-Slicer软件计算血肿体积，以术后1 d血肿体积为基线，以术后28 d血肿吸收率作为主要疗效指标。采用单因素方差分析及多元线性回归分析评估ApoE基因型与血肿吸收率的相关性，校正年龄、基线血肿体积等混杂因素。结果 152例患者中，ApoE基因型分布为：ε2/ε3型28例（18.4%）、ε3/ε3型99例（65.1%）、ε3/ε4型25例（16.5%），符合Hardy-Weinberg平衡（χ2=1.320,P=0.250）。三组基线临床特征差异无统计学意义（P>0.05）。血肿吸收率比较显示：ε2/ε3组[（42.3±8.1）%]显著高于ε3/ε4组[（28.5±6.9）%;P<0.001];ε3/ε3组为（35.6±7.3）%，介于两者之间。多元线性回归分析显示：ε2等位基因是血肿吸收率的独立正向预测因子（β=0.314,95%CI:0.120～0.510,P=0.001），而ε4等位基因呈独立负向关联（β=-0.217,95%CI:-0.390～-0.040,P=0.015）。亚组分析发现年龄与ε2等位基因存在交互作用（β=-0.180,P=0.038）,>60岁患者中ε2的促吸收效应有所减弱。结论 ApoE ε2等位基因可显著增强阿托伐他汀促进SSDH术后血肿吸收的疗效，而ε4等位基因则可能减弱该药物作用。ApoE基因型有望成为指导SSDH患者阿托伐他汀个体化治疗的潜在遗传标志物，ε4携带者可能需要调整治疗方案。

Objective To investigate the correlation between apolipoprotein E(ApoE) gene polymorphisms and the efficacy of atorvastatin in promoting the absorption of residual hematoma after burr-hole drainage for subacute subdural hematoma(SSDH), thereby providing a genetic basis for personalized treatment. Methods A retrospective analysis was conducted on clinical data from 152 SSDH patients admitted to the Department of Neurosurgery, The First People's Hospital of Foshan, from January 2020 to June 2024. All patients underwent burr-hole drainage, received regular atorvastatin treatment(20 mg/d, ≥4 weeks), and had ApoE genotyping results. ApoE genotyping was performed using the PCR-RFLP method. Hematoma volumes were calculated using 3D-Slicer software, with the volume on postoperative day 1 as the baseline. The primary efficacy indicator was the hematoma absorption rate on postoperative day 28. One-way ANOVA and multiple linear regression analyses were used to evaluate the correlation between ApoE genotypes and the hematoma absorption rate, adjusting for confounding factors such as age and baseline hematoma volume. Results Among the 152 patients, the distribution of ApoE genotypes was: ε2/ε3 in 28 cases(18.4%), ε3/ε3 in 99 cases(65.1%), and ε3/ε4 in 25 cases(16.5%), which was consistent with the Hardy-Weinberg equilibrium(χ2=1.320, P=0.250). There were no statistically significant differences in baseline clinical characteristics among the three groups(P>0.05). Comparison of hematoma absorption rates showed that the ε2/ε3 group [(42.3±8.1)%] had a significantly higher rate than the ε3/ε4 group [(28.5±6.9)%; P<0.001]; the ε3/ε3 group [(35.6±7.3)%] fell in between. Multiple linear regression analysis revealed that the ε2 allele was an independent positive predictor of the hematoma absorption rate(β=0.314, 95% CI: 0.120～0.510, P=0.001), while the ε4 allele showed an independent negative association(β=-0.217, 95% CI:-0.390～-0.040, P=0.015). Subgroup analysis indicated an interaction between age and the ε2 allele(β=-0.180, P=0.038), where the pro-absorptive effect of ε2 was attenuated in patients over 60 years old. Conclusion The ApoE ε2 allele can significantly enhance the efficacy of atorvastatin in promoting hematoma absorption after SSDH surgery, whereas the ε4 allele may weaken this drug effect. The ApoE genotype holds promise as a potential genetic marker to guide personalized atorvastatin treatment for SSDH patients, suggesting that alternative treatment strategies might be necessary for ε4 carriers.