血管性认知功能障碍与雄激素受体基因启动子区甲基化状态、同型半胱氨酸水平的相关性研究

Association of vascular cognitive impairment with methylation status of the promoter region of androgen receptor gene and homocysteine level

摘要:

目的 检测血管性认知功能障碍（VCI）患者的雄激素受体（AR）基因启动子区CpG岛甲基化状态和同型半胱氨酸（HCY）水平，从分子水平探讨VCI与AR基因启动子高甲基化、HCY的关系。方法 采用病例对照研究方法，选取脑卒中慢性期的VCI患者46例组成病例组，随机选取年龄相同的健康人92例组成对照组。MSP法和RT-PCR法检测研究对象AR启动子区CpG岛的甲基化状态及mRNA表达水平，采用酶转换免疫法检测HCY水平。结果 VCI患者中甲基化率为71.74%，对照组患者中甲基化率为19.57%，病例组与对照组甲基化率相比较，差异有统计学意义（P<0.05）。VCI组患者较对照组患者AR基因mRNA表达缺失5.24倍，两组患者AR基因mRNA表达缺失率比较，差异有统计学意义（P<0.05）。病例组HCY水平为14.73±5.31，对照组为7.12±4.19，病例组显著高于对照组，差异有统计学意义（P<0.05）。AR基因启动子区甲基化程度与HCY相关系数为r=0.534，差异具有统计学意义（P<0.05）；随HCY水平升高，病例组甲基化程度亦递次升高。结论 AR基因启动子区高甲基化与VCI发病相关；高HCY水平与AR基因启动子区高甲基化相关。

Abstract:

Objective To investigate the methylation status of the promoter region of androgen receptor (AR) gene and homocysteine (Hcy) level in patients with vascular cognitive impairment (VCI), as well as the association of VCI with a high methylation level of the promoter region of AR gene and Hcy level.Methods A case-control study was performed. A total of 46 VCI patients in the chronic period of stroke were enrolled as case group, and 92 healthy persons matched for age were enrolled as control group. Methylation-specific PCR and RT-PCR were used to determine the methylation status of the CpG islands in the promoter region of AR gene and measure the mRNA expression of AR gene, and enzymic transformation was used to measure the Hcy level.Results There was a significant difference in methylation rate between the case group and the control group (71.74% vs 19.57%, P<0.05). The mRNA expression of AR gene in the case group was 5.24 times lower than that in the control group, and there was a significant difference in the loss rate of mRNA expression of AR gene between the two groups (P<0.05). The case group had a significantly higher Hcy level than the control group (14.73±5.31 vs 7.12±4.19, P<0.05). The methylation level of the promoter region of AR gene was significantly correlated with Hcy level (r=0.534); in the case group, the methylation level increased with the increasing Hcy level.Conclusions A high methylation level of the promoter region of AR gene is associated with the pathogenesis of VCI, and a high Hcy level is associated with the high methylation level of the promoter region of AR gene.