Alzheimer病患者载脂蛋白E基因多态性及线粒体DAN4336突变的研究

Study on apolipoprotein E gene polymorphism and mtDAN4336 mutation in patients with Alzheimer's disease

目的 研究散发性Alzheimer病 (AD)患者载脂蛋白E (ApoE)基因型的分布以及线粒体DAN4 336基因突变情况 ,并对不同国家和地区AD患者ApoE基因型的分布频率进行对比。方法 采用聚合酶链反应 限制性片段长度多态性分析 (PCR RFLP)方法对 12 7例AD患者 (AD组 )和 138名正常老年人 (正常组 )ApoE基因型和mtDNA基因突变进行分析。结果 AD组携带 2个、1个和不含ApoE 4基因型的比例为 2 4 %、18 1%和 79 5 % ;正常组的比例分别为 0 7%、10 1%和 89 2 % ,两组比较差异有显著性 (P <0 0 5 ) ;两组均未出现mtDNA 4 336基因突变。AD组ε4 /4比例相对于西方研究报道要低 ,与部分亚洲国家研究相近。结论 ApoE 4等位基因可能是中国散发性AD发生的危险因素 ,ApoE基因型分布频率可能与人群选择、病例分辨和种族、地区差异有关。

Objective To study the distribution of Apolipoprotein E(ApoE) gene polymorphism and mtDAN*!4336 mutation in patients with sporadic Alzheimer's disease(AD),and analyse the difference of frequency of ApoE genotype from some other studies.Methods The polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) technique was used to analyze the ApoE allele genotype and mtDAN mutation of 127 AD patients and 138 healthy elderly controls.Results In AD group, we found 2.4% of the patients with 2 ApoE4 allele gene, 18.1% of the patients with 1 ApoE4 allele gene, and 79.5% of the patients without ApoE4 allele gene. However, in control group, the frequency was 0.7%, 10.1% and 89.2% respectively. There was a significant difference between the two groups( P<0.05). Mitochondrial DAN(mtDAN*!4336) mutation was not found in either AD group or control group.Although the results were similar with some reports from Asia, the ratio of ApoEε4/4 in AD was lower than many other reports from West.Conclusion Our study indicates that ApoEε4 allele gene is a genetic risk factor for Chinese sporadic AD, and distribution frequency of ApoE genotype may be related to people excerpt, case discrimination, race and area.