分拣蛋白相关受体L1基因异常甲基化在晚发散发性阿尔茨海默病中的研究

Correlation between sortilin-related receptor 1 gene promoter hypermethylation and Alzheimer's disease

目的研究分拣蛋白相关受体L1(sortilin-related receptor 1,SORL1)基因启动子区异常甲基化与阿尔茨海默病(AD)发生的相关性。方法选择晚发散发性AD(SAD)患者40例为SAD组,另选择健康体检者8例为对照组。提取外周血DNA,设计硫化测序PCR引物以及甲基化特异性PCR引物,进行PCR扩增以及测序分析。结果对照组3例和SAD组3例经硫化修饰以及PCR扩增,对照组SORL1基因甲基化率分别为1.5%、1.0%、1.0%,SAD组SORL1基因甲基化率分别为74.0%、70.5%、73.0%。甲基化特异性PCR分析结果显示,SORL1基因在8例健康人中呈完全非甲基化状态,在40例SAD患者中其甲基化阳性例数为21例,甲基化阳性率为52.5%(P<0.05)。结论 SORL1基因启动子区异常甲基化可能参与SAD的发生,为疾病的早期监测提供可能的分子理论依据。

Objective To study the correlation between sortilin-related receptor 1 （SORL1）gene promoter hypermethylation and Alzheimer＇s disease（AD）. Methods Forty patients with sporadic AD（SAD）served as a SAD group and 8 healthy subjects served as a control group in this study. DNA was isolated from peripheral blood. BSP and MSP primers were designed for PCR. The SORL1 gene was amplified and sequencd by PCR. Results The SORL1 gene,isolated from 3 subjects in control group and from 3 patients in SAD group,was methylated and amplified by PCR, with a methylation rate of 1.5%,1.0%,1.0% respectively in control group and 74.0%,70.5%, 73.0% respectively in SAD group. PCR showed that the SORL1 gene was unmethylated in 10 health subjects and methylated in 40 SAD patients with a positive methylation rate of 52.5 % （P〈 0.05）. Conclusion The SORL1 gene promoter hypermethylation may be involved in occurrence of SAD,thus providing the molecular evidence in theory for its early monitoring.