载脂蛋白E基因多态性与脑淀粉样血管病相关脑出血风险：Meta分析和系统评价

Meta-Analysis and Systematic Review of the Association between Apolipoprotein E Gene Polymorphism and Risk of Cerebral Hemorrhage in Cerebral Amyloid Angiopathy

摘要: 背景和目的：脑淀粉样血管病(Cerebral amyloid angiopathy, CAA)是一种脑小血管疾病，可导致自发性脑出血，短暂局灶性神经系统发作，认知下降或痴呆。我们系统地回顾了载脂蛋白E (Apolipo-protein E, APOE)基因多态性和CAA相关脑出血(cerebral amyloid angiopathy-intracerebral hemor-rhage, CAA-ICH)相关的文章，以更好地明确二者的关系。方法：我们检索了PubMed，Embase，Scopus，Cochrane图书馆和Google学术等数据库已发表文献中英文文章，检索时间截至2022年9月。通过计算包括显性模型、隐性模型、纯合子模型、杂合子模型、加性模型和等位基因模型等6种遗传模型的合并比值比(odds ratios, ORs)及其95%置信区间(95% confidence interval, 95% CI)来评估基因型的影响。结果：本研究纳入6项符合条件的研究，包括429名CAA-ICH患者。APOE ɛ2:ɛ3多态性和CAA-ICH分析结果表明，显性模型(OR = 3.24, 95% CI: 1.65~6.34, P = 0.0006 < 0.01)、杂合子模型(OR = 3.09, 95% CI: 1.52~6.26, P = 0.002 < 0.01)、纯合子模型(OR = 3.24, 95% CI: 1.35~7.75, P = 0.008 < 0.01)和等位基因模型(OR = 2.51, 95% CI: 1.92~3.29, P < 0.00001)等差异具有统计学意义。APOE ɛ4:ɛ3多态性和CAA-ICH的荟萃结果明确表明，在显性模型(OR = 1.87, 95% CI: 1.01~3.48, P = 0.05)，隐性模型(OR = 3.73, 95% CI: 1.98~7.02, P < 0.0001)，纯合子模型(OR = 3.91, 95% CI: 2.27~6.75, P < 0.0001)和等位基因模型(OR = 2.01, 95% CI: 1.3~3.12, P = 0.002 < 0.01)下与CAA-ICH存在显著关联。结论：APOE ɛ2、ɛ4与CAA-ICH风险显著相关。需要进一步大样本研究验证这一发现。

Abstract: Background and Objective: Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease that can cause spontaneous brain hemorrhage, transient focal neurological episodes, cognitive de-cline or dementia. We conducted a systematic review of articles on the association between apolipoprotein E (APOE) gene polymorphism and cerebral amyloid angiopathy-related intracere-bral hemorrhage (CAA-ICH) to better understand their relationship. Methods: We searched several databases including PubMed, Embase, Scopus, Cochrane Library, and Google Scholar for published articles in English and Chinese. The search was conducted up to September 2022. We assessed the influence of genotypes by calculating the pooled odds ratios (ORs) and their 95% confidence inter-val (CI) for six genetic models including dominant model, recessive model, homozygous model, het-erozygous model, additive model, and allelic model. Result: Six eligible studies were included, in-volving 429 patients with CAA-ICH. The analysis of APOE ε2:ε3 polymorphism and CAA-ICH showed significant differences in dominant model (OR = 3.24, 95% CI: 1.65~6.34, P = 0.0006 < 0.01), heter-ozygous model (OR = 3.09, 95% CI: 1.52~6.26, P = 0.002 < 0.01), homozygous model (OR = 3.24, 95% CI: 1.35~7.75, P = 0.008 < 0.01), and allele model (OR = 2.51, 95% CI: 1.92~3.29, P < 0.00001). The meta-analysis results of APOE ε4:ε3 polymorphism and CAA-ICH clearly indicated significant asso-ciations under dominant model (OR = 1.87, 95% CI: 1.01~3.48, P = 0.05), recessive model (OR = 3.73, 95% CI: 1.98~7.02, P < 0.0001), homozygous model (OR = 3.91, 95% CI: 2.27~6.75, P < 0.0001), and allele model (OR = 2.01, 95% CI: 1.3~3.12, P = 0.002 < 0.01) with CAA-ICH. Conclusion: APOE ɛ2 and ɛ4 are significantly associated with the risk of CAA-ICH. Further large-scale studies are needed to validate this finding.