基础医学与临床 ›› 2015, Vol. 35 ›› Issue (11): 1476-1480.

• 研究论文 • 上一篇    下一篇

MEF2A启动子多态性对转录活性及冠心病易感性的影响

刘本荣1,熊玉娟2,钟赟1,莫沛1,李爱群1,熊龙根1   

  1. 1. 广州医科大学附属第二医院
    2. 广州中医药大学第二临床学院
  • 收稿日期:2015-06-11 修回日期:2015-07-23 出版日期:2015-11-05 发布日期:2015-11-03
  • 通讯作者: 刘本荣 E-mail:liubenrong@gzhmu.edu.cn
  • 基金资助:
    MEF2 在细胞衰老中的调节作用及机制研究;转录因子MEF的遗传变异与冠心病的相关性及机制研究;冠心病的易感性与人类白细胞抗原多态性的关联研究

Effects of the polymorphisms in MEF2A promoter on the transcription activity and the susceptibility to coronary artery disease

  • Received:2015-06-11 Revised:2015-07-23 Online:2015-11-05 Published:2015-11-03
  • Contact: Benrong Liu E-mail:liubenrong@gzhmu.edu.cn

摘要: 目的 研究MEF2A启动子多态性对其转录活性的影响及与冠心病(CAD)易感性的关系。方法 CAD患者44例,正常对照45例,用DNA测序鉴定MEF2A启动子区的单核苷酸多态性(SNP),以克隆测序确定启动子单倍型,采用双萤光素酶报告基因系统评价不同启动子单倍型的转录活性,比较两组中的单倍型频率及纯合率差异。结果 发现9个SNPs,它们组成18种单倍型,其中H1(16.29%)、H5(17.42%)、H8(16.85%)和H16(28.65%)的频率较高,占总数的79.21%。H5和H8的转录活性最高,H9次之,其它单倍型的活性较低。-580(C -> A)、-646(G -> T)和-948(C -> T)位点的碱基改变导致转录因子结合位点(TFBS)丢失。由-948(C/T)、-646(G/T)和-580(C/A)组成的单倍型有CGC(17.98%)、CGA(3.94%)、TGA(36.51%)、TTC(33.15%)、TTA(3.94%)、TGC(3.37%)和CTC(1.69%),其中包含TGA的单倍型的转录活性最高。CAD组中MEF2A启动子纯合率显著高于对照组(P < 0.05)。结论 MEF2A启动子区的SNPs导致TFBS改变,不同单倍型具有转录活性差异,其启动子纯合率与CAD易感性呈正相关。

关键词: 肌细胞增强因子2A, 启动子, SNP, 转录因子结合位点

Abstract: Objective To explore the influence of the polymorphisms in the promoter of myocyte enhancer factor 2A (MEF2A) on the promoter activity, and the relationship of the polymorphisms with the susceptibility to coronary artery disease (CAD). Methods Forty-four CAD patients and 45 controls were enrolled. The single nucleotide polymorphisms (SNPs) in the promoter of MEF2A and the promoter haplotypes were identified with cloning and Sanger DNA sequencing. The transcription activity of the different promoter haplotypes were determined with dual luciferase reporter system. The frequency of the haplotypes and the homozygosity were compared between CAD and control group. Results Nine SNPs were found, and they combined into 18 haplotypes. H1(16.29%)、H5(17.42%)、H8(16.85%) and H16(28.65%)are the most popular haplotypes, and take 79.21% of the total. H5 and H8 showed the highest transcription activity, and H9 was next, the others were relative weak. Three SNPs, -580(C -> A), -646(G -> T) and -948(C -> T), cause a loss of predicted transcription factor binding site (TFBS). The haplotypes clustered with this 3 SNPs and the frequency was shown as follow: CGC(17.98%)、CGA(3.94%)、TGA(36.51%)、TTC(33.15%)、TTA(3.94%)、TGC(3.37%)、CTC(1.69%). The haplotype with TGA showed the strongest transcription activity. The homozygosity in CAD group is markedly higher than that in the control group (P < 0.05). Conclusion The SNPs in the promoter of MEF2A may lead to change of TFBS. The different haplotypes have distinct promoter activity, and the homozygosity of MEF2A promoter may contribute to a higher susceptibility to CAD.

Key words: Myocyte enhancer factor 2A, Promoter, SNP, Transcription factor binding site

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