老年痴呆患者的危险因子载脂蛋白E4的研究

Apolipoprotein E 4 gene is a risk factor for Alzheimer′s disease

目的 研究Alzheimer病 (AD)与载脂蛋白E(ApoE)基因ε4的相互关系 ,为AD的实验室诊断提供可能的外周生物学指标。方法 我们收集了 10 7例AD患者、68例血管性痴呆 (VD)患者及74例年龄、性别相匹配的健康对照组 (NDC)。均取外周血抗凝 ,酚、氯仿法提取DNA采用聚合酶链反应 (PCR)和限制性片段长度多态性 (RFLP)分析技术检测ApoE基因型。结果 AD患者中ApoEε4等位基因频率明显高于VD及NDC组 (P <0 0 1) ,而VD患者ε4等位基因频率与NDC组间差异无显著性 (P >0 0 5 )。在AD患者中 ,ε4纯合子基因型者的发病年龄较ε4杂合子基因型者明显年轻、ε4杂合子基因型携带者的发病年龄较非ε4基因携带者明显年轻 (P值均 <0 0 5 ) ,而VD患者的发病年龄与是否携带ε4等位基因无明显相关性。本研究还发现 3例携有ApoEε4 / 4基因型的家族性痴呆患者。结论 ApoEε4与AD密切相关 ,是AD的危险因子。

Objective To study the association of Alzheimer disease (AD) with apolipoprotein E (ApoE) ε4 allele and to find the biological peripheral markers for the laboratory diagnosis of AD. Methods 107 patients with AD, 68 patients with vascular dementia (VD) and 74 sex- and age-matched non-demented healthy individuals (NDC) were collected. DNA from patients and nealthy individuals was extracted from peripheral blood samples with the phenol-chloroform procedure and ApoE was investigated with the methods of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results The frquency of ε4 was significantly higher in AD than that in VD and NDC and there was no difference in the frequency of ε4 between VD and NDC. The age at onset of the disease in the group carrying two ε4 alleles was significantly younger than that in the group with one ε4 allele in AD. Morreover, in comparison with AD patients without ε4 allele, the age at onset in the group with one ε4 allele was younger. Patients with ε4 or without ε4 allel in VD patients did not differ significantly in age at oneset. Meanwhile, 3 familial AD cases were found, all carrying ε4 allele. Conclusion AD and ApoE4 were closely related. ApoE ε4 was a dangerous factor of AD and ApoE 4 allele made contribution to the heterogenicity of AD.