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高同型半胱氨酸血症对雌激素受体α基因甲基化修饰的影响及其与脑梗死发病的关系

Effects of homocysteine on the methylation status of the estrogen receptor α gene promoter and the relationship with the pathogenesis of cerebral infarction

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【作者】 杨志甫王丽珍孟祥君张茂林席富强

【Author】 YANG Zhi-fu1,WANG Li-zhen,MENG Xiang-jun,ZHANG Mao-lin,XI Fu-qiang(1 First Afficiated Hospital of Baotou Medical College,Baotou 014010,P.R.China)

【机构】 包头医学院第一附属医院包头医学院病理教研室

【摘要】 目的探讨雌激素受体α(ER-α)基因启动子区甲基化状态与脑梗死发病的关系,同时探讨高同型半胱氨酸血症作为脑梗死独立危险因素的致病机制。方法选择106例脑梗死患者作为观察组,47例健康体检者作为正常对照组。检测两组血同型半胱氨酸(tHcy)浓度,并采用巢式甲基化特异性PCR法检测其ER-α基因启动子区甲基化状态。结果观察组tHcy浓度及ER-α基因启动子区甲基化发生率明显高于正常对照组(t=7.019,P=0.00;χ2=22.27,P=0.00)。Spearman秩相关分析结果显示,脑梗死患者ER-α基因启动子区甲基化状态与tHcy浓度呈高度正相关(r=0.733,P=0.00)。结论高同型半胱氨酸血症很可能通过干扰ER-α基因的甲基化状态而成为脑梗死独立危险因素的致病机制。

【Abstract】 Objective To investigate the relationship between cerebral infarction and alteration of the methylation status of the estrogen receptor α gene promoter and the mechanism of high homocysteine as an independent risk factor of cerebral infarction.Methods 106 cerebral infarction patients and 47 healthy people were selected for this research.Detecting the level of total plasmahomoeysteine(tHcy) was detected.The methylation status of CPG islands in ER-α gene promoter region was detected by nested-methylation-specific PCR(nMSP).Be using spearman rank correlation,the relationship between the level of tHcy and the methylation status of ER-α gene promoter region was analyzed.Results The level of tHcy,and the methylation frequency of ER-α gene promoter region in the cerebral infarction patients were much higher than those in the healthy people(t=7.019,P=0.00;χ2=22.27,P=0.00).In the cerebral infarction patients,the spearman rank correlation explored an obvious correlation between the level of tHcy and the methylation status of ER-α gene promoter region(r=0.733,P=0.00).Conclusions High homocysteine can lead to the hypermethylation of ER-α gene,downregulate the expression of ER-α gene,and let the estrogen lose protection of resisting cerebral infarction.

【基金】 包头医学院秦文斌科技教育基金资助项目(200905);包头市社会发展科技支撑项目(2010S2001-1-2)
  • 【文献出处】 山东医药 ,Shandong Medical Journal , 编辑部邮箱 ,2011年41期
  • 【分类号】R743.32
  • 【被引频次】11
  • 【下载频次】155
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