SIRT7基因表达调控与急性心肌梗死的分子遗传学研究

发布时间：2018-05-14 15:22

本文选题：SIRT7基因启动子 + 冠心病　；参考：《济宁医学院》2017年硕士论文

【摘要】：目的:冠状动脉粥样硬化性心脏病(Coronary artery disease,CAD)是一种临床常见的病因复杂的心血管疾病,可影响心脏的冠状动脉供血,导致心肌缺血缺氧而引起的心脏病,冠心病的患者有发展为心肌梗死的风险,急性心肌梗死属冠心病的严重类型。冠心病的发病归因于环境与遗传因素的相互作用。近年来,越来越的证据显示相关基因的遗传多态性与冠心病的发病风险相关,据相关研究的数据显示,与冠心病相关的等位基因位点有50多个,但是这些基因变异仅能解释约10%的冠心病病例。因此,我们推测相关基因低频和罕见的遗传变异可能成为冠心病的病因,尤其是急性心肌梗死。SIRT7是高度保守的NAD+依赖的去乙酰化酶sirtuins家族成员之一,是许多细胞活动的关键调控因子,参与调控多种生命进程,包括细胞增殖、基因组的稳定性、代谢平衡、应激反应、衰老和肿瘤的发生等,可参与恶性肿瘤、心血管疾病、脂肪肝及糖尿病等疾病的进程。根据SIRT7在心血管疾病中的作用,以及调节细胞生存和凋亡、脂质代谢的过程,我们推测SIRT7基因启动子调控区域的DNA序列变异(DSVs)会引起SIRT7基因表达水平的变化,可能参与冠心病的发生与发展。方法:采用大样本和病例对照研究,AMI病人424例,健康对照人群341例,通过外周血白细胞DNA提取、PCR扩增SIRT7基因启动子区域、DNA目的片段送测序,根据测序结果分析AMI组和对照组SIRT7基因启动子调控区域的DNA序列变异情况,进行SIRT7基因启动子区域的遗传学分析和研究。结果:在本研究中,我们一共发现了8个DNA变异序列,其中包括1个单核苷酸多态性(SNPs),1个杂合子缺失变异序列和6个杂合子单碱基变异序列。其中在4名AMI患者发现3个杂合子序列变异g.2069TC,g.2183CT,g.2463AT和1个杂合子缺失变异g.2555del,而在对照组中并没有发现。结论:本研究提示,在急性心肌梗死病人中,DNA序列变异可能改变了SIRT7基因启动子的转录活性,从而改变了SIRT7基因的表达水平,使SIRT7基因的功能发生改变,最终促进了急性心肌梗死的发生和发展。
[Abstract]:Objective: coronary artery disease (CAD) is a common cardiovascular disease with complicated etiology, which can affect the coronary blood supply of the heart and lead to heart disease caused by myocardial ischemia and hypoxia. Patients with coronary heart disease are at risk of developing myocardial infarction, which is a serious type of coronary heart disease. The pathogenesis of coronary heart disease is attributed to the interaction between environment and genetic factors. In recent years, there has been increasing evidence that genetic polymorphisms of related genes are associated with the risk of coronary heart disease. According to the data from related studies, there are more than 50 allelic loci associated with coronary heart disease. But these mutations only account for about 10% of cases of coronary heart disease. Therefore, we speculate that the low frequency and rare genetic variation of the associated genes may be the cause of coronary heart disease, especially the acute myocardial infarction. SIRT7 is a member of the highly conserved NAD dependent sirtuins family of deacetylase. Is a key regulator of many cell activities, involved in regulating a variety of life processes, including cell proliferation, genomic stability, metabolic balance, stress response, aging, tumorigenesis, and so on, involved in malignant tumors, cardiovascular disease, etc. The progression of diseases such as fatty liver and diabetes. Based on the role of SIRT7 in cardiovascular disease and the regulation of cell survival, apoptosis and lipid metabolism, we speculate that the DNA sequence variation in the regulatory region of SIRT7 gene promoter may cause changes in the expression of SIRT7 gene. May be involved in the occurrence and development of coronary heart disease. Methods: 424 patients with AMI and 341 healthy controls were studied with large sample and case control. The SIRT7 promoter region was amplified by DNA extraction from peripheral blood leukocytes and sequenced. According to the results of sequencing, the variation of DNA sequence in the promoter region of SIRT7 gene in AMI group and control group was analyzed, and the genetic analysis and study of the promoter region of SIRT7 gene were carried out. Results: in this study, we found a total of 8 DNA mutation sequences, including a single nucleotide polymorphism (SNPs), a heterozygote deletion mutation sequence and 6 heterozygote single base mutation sequences. Three heterozygotes were found in 4 patients with AMI and one heterozygote deletion variation, g.2555del. was found in 4 patients with AMI, and no heterozygous mutation was found in the control group. Conclusion: this study suggests that DNA sequence variation in patients with acute myocardial infarction may change the transcriptional activity of SIRT7 gene promoter, thus change the expression level of SIRT7 gene and the function of SIRT7 gene. Finally, it promotes the occurrence and development of acute myocardial infarction.
【学位授予单位】：济宁医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R542.22

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