ERа-A 基因的高甲基化和高血清同型半胱氨酸水平与脑白质高信号患者的认知障碍相关。

Hypermethylation of ERа-A gene and high serum homocysteine level are correlated with cognitive impairment in white matter hyperintensity patients.

机构信息

Department of Neurology, the First Affiliated Hospital, Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

出版信息

QJM. 2019 May 1;112(5):351-354. doi: 10.1093/qjmed/hcz031.

DOI:10.1093/qjmed/hcz031

PMID:30690641

Abstract

OBJECTIVE

To investigate the methylation status in promoter region of estrogen receptor alpha (ERа)-A gene and its relation with plasma homocysteine (Hcy) level and cognitive impairment in white matter hyperintensity (WMH) patients.

PATIENTS AND METHODS

210 patients aged 65 and older were selected. The methylation status of CpG islands in ERа-A gene promoter was analyzed by nested methylation-specific PCR. Serum Hcy and estradiol levels were measured by enzyme-linked immunosorbent assay. Cognitive function were evaluated using minimum mental state examination, the montreal cognitive assessment, Stroop color-word test, symbol digit modalities, trail making test B and instrumental activities of daily living (IADL). The severity of WMH was evaluated with the Fazekas scale by brain magnetic resonance imaging.

RESULTS

We found a significant association between the severity of WMH and CpG island methylation of ERа-A gene (P < 0.05). Multiple regression analysis showed that serum Hcy level, methylation of ERа-A gene and WMH severity were significant determining factors for cognitive impairment (P < 0.05). The spearman rank correlation analysis showed a significant correlation of methylation of ERа-A gene with serum Hcy level, WMH severity, cognitive function and IADL status (P < 0.05).

CONCLUSION

Methylation of ERа-A gene promoter has a high frequency in WMH patients with cognitive impairment and is correlated with high plasma Hcy level.

摘要

目的

研究雌激素受体 α（ERа）-A 基因启动子区甲基化状态及其与脑白质高信号（WMH）患者血浆同型半胱氨酸（Hcy）水平和认知障碍的关系。

方法

选取 210 例 65 岁以上患者。采用巢式甲基化特异性 PCR 分析 ERа-A 基因启动子区 CpG 岛的甲基化状态。采用酶联免疫吸附试验测定血清 Hcy 和雌二醇水平。采用简易精神状态检查、蒙特利尔认知评估、Stroop 色词测验、符号数字模式测验、连线测验 B 和日常生活活动能力量表（IADL）评估认知功能。采用脑磁共振成像 Fazekas 量表评估 WMH 严重程度。

结果

我们发现 WMH 严重程度与 ERа-A 基因 CpG 岛甲基化之间存在显著相关性（P<0.05）。多元回归分析显示，血清 Hcy 水平、ERа-A 基因甲基化和 WMH 严重程度是认知障碍的显著决定因素（P<0.05）。Spearman 秩相关分析显示，ERа-A 基因甲基化与血清 Hcy 水平、WMH 严重程度、认知功能和 IADL 状态呈显著相关（P<0.05）。