摘要：

目的: 探讨APOE基因多态性对阿托伐他汀治疗慢性硬膜下血肿的临床疗效。方法: 纳入2022年1月至2023年12月广东省佛山市第一人民医院收治的104例慢性硬膜下血肿患者，采用实时荧光定量聚合酶链反应对DNA样本进行APOE基因检测，并按照APOE基因型分为APOE2型组（9例）、APOE3型组（58例）、APOE4型组（37例）。给予所有患者口服阿托伐他汀治疗3个月，比较3组临床疗效，健康状态[Karnofsky功能状态评分（KPS）]、血肿清除、并发症及复发情况。结果: 3组总有效率（Fisher确切概率法：P = 0.011）和复发率（Fisher确切概率法：P = 0.046）的比较差异具有统计学意义，进一步两两比较，APOE3型组总有效率高于（Fisher确切概率法：P = 0.045）、复发率低于（Fisher确切概率法：P = 0.045）APOE2型组。3组KPS评分、血肿量及血肿面积比较差异具有统计学意义（均P = 0.000），进一步组间两两比较，治疗前APOE3型组较APOE2型组KPS评分高（P = 0.009）、血肿量（P = 0.000）和血肿面积（P = 0.000）大，且APOE4型组较APOE2型组血肿量大（P = 0.038）；治疗后1个月APOE3型组KPS评分高于APOE2型组（P = 0.000）和APOE4型组（P = 0.000），血肿量和血肿面积均小于APOE2型组（P = 0.000，0.000）和APOE4型组（P = 0.000，0.000）；治疗后3个月APOE3型组KPS评分高于（P = 0.007）、血肿面积小于（P = 0.046）APOE2型组。组内不同观察时间点两两比较发现，APOE2型组、APOE3型组和APOE4型组治疗后1个月KPS评分高于治疗前（P = 0.000，0.000，0.000），治疗后3个月KPS评分高于治疗前（P = 0.000，0.000，0.000）和治疗后1个月（P = 0.001，0.000，0.000）；3组治疗后1个月血肿量（P = 0.000，0.000，0.000）和血肿面积（P = 0.000，0.000，0.000）小于治疗前，治疗后3个月血肿量和血肿面积小于治疗前（血肿量：P = 0.000，0.000，0.000；血肿体积：P = 0.000，0.000，0.000）和治疗后1个月（血肿量：P = 0.002，0.000，0.000；血肿体积：P = 0.000，0.000，0.000）。KPS评分、血肿量及血肿面积的处理因素与测量时间之间存在相互作用（均P = 0.000），APOE3型组KPS评分、血肿量及血肿面积变化幅度最大，提示APOE3型患者对阿托伐他汀的治疗反应最佳，疗效最好。结论: APOE基因多态性与慢性硬膜下血肿患者口服阿托伐他汀疗效关系密切，且APOE3型患者表现出最佳疗效和安全性，有助于慢性硬膜下血肿个性化治疗方案的制定。

关键词: 血肿，硬膜下，慢性, 载脂蛋白E类, 多态现象，遗传, 阿托伐他汀

Abstract:

Objective: To explore the effect ofAPOEgene polymorphism on the clinical efficacy combined with oral atorvastatin in the treatment of chronic subdural hematoma (CSDH). Methods: A total of 104 patients with CSDH admitted in The First People's Hospital of Foshan from January 2022 to December 2023 were selected as the research subjects. TheAPOEgene of the extracted DNA samples of the patients was detected by real - time fluorescence quantitative polymerase chain reaction (PCR) technology, and 104 patients were divided into APOE2 type group (n = 9), APOE3 type group (n = 58) and APOE4 type group (n = 37) according to the genotype. All patients were treated with oral atorvastatin therapy for 3 months. The clinical efficacy, health status [Karnofsky Performance Status (KPS)], hematoma clearance, complication and recurrence of each group were compared. Results: The total effective rate (Fisher's exact probability: P = 0.011) and recurrence rate (Fisher's exact probability: P = 0.046) among the 3 groups were statistically significant. Further pairwise comparison showed that the total effective rate of APOE3 type group was higher (Fisher's exact probability: P = 0.045) and the recurrence rate was lower (Fisher's exact probability: P = 0.045) than the APOE2 type group. There were significant differences in KPS score, hematoma volume and hematoma area among the 3 groups (P = 0.000, for all). Further pairwise comparison between the groups showed that the APOE3 type group had higher KPS score (P = 0.009), larger hematoma volume (P = 0.000) and hematoma area (P = 0.000) before treatment than the APOE2 type group. The APOE4 type group had a larger hematoma volume than the APOE2 type group (P = 0.038). After one month of treatment, the KPS score of APOE3 type group was higher than that of APOE2 type group (P = 0.000) and APOE4 type group (P = 0.000), and the hematoma volume and hematoma area of APOE3 type group were smaller than those of APOE2 type group (P = 0.000, 0.000) and APOE4 type group (P = 0.000, 0.000). At the 3 months treatment, the KPS score of APOE3 type group was higher than that of APOE2 type group (P = 0.007), and the hematoma area was smaller than that of APOE2 type group (P = 0.046). Comparison of the same group at different observation time points showed that the KPS scores of APOE2 type group, APOE3 type group and APOE4 type group at one month after treatment were higher than those before treatment (P = 0.000, 0.000, 0.000), and the KPS scores at 3 months of treatment were higher than those before treatment (P = 0.000, 0.000, 0.000) and one month after treatment (P = 0.001, 0.000, 0.000); the hematoma volume (P = 0.000, 0.000, 0.000) and hematoma area (P = 0.000, 0.000, 0.000) at one month of treatment in the 3 groups were lower than those before treatment, and the hematoma volume and hematoma area at 3 months of treatment were lower than those before treatment (hematoma volume: P = 0.000, 0.000, 0.000; hematoma volume: P = 0.000, 0.000, 0.000) and one month after treatment (hematoma volume: P = 0.002, 0.000, 0.000; hematoma volume: P = 0.000, 0.000, 0.000). There was an interaction between the treatment factors of KPS score, hematoma volume and hematoma area and the measurement time (P = 0.000, for all). The changes of KPS score, hematoma volume and hematoma area in APOE3 type group were the largest, suggested that the APOE3 type group had the largest response to atorvastatin treatment and the best treatment effect. Conclusions: The polymorphism of the APOE gene is closely related to the therapeutic effect of oral atorvastatin in patients with CSDH, and patients with APOE3 type show the best efficacy and safety, which is help for the formulation of personalized treatment plans for CSDH.

Key words: Hematoma, subdural, chronic, Apolipoproteins E, Polymorphism, genetic, Atorvastatin