Genetic analysis of the SIRT1 gene promoter in myocardial infarction
Genetic analysis of the SIRT1 gene promoter in myocardial infarction
复制标题
心肌梗死SIRT1基因启动子的遗传分析
DOI：
10.1016/j.bbrc.2012.08.071
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发表时间：
2012-09-21
影响因子：
3.1
通讯作者：
Yan, Bo
中科院分区：
文献类型：
--
作者：
Cui, Yinghua;Wang, Haihua;Yan, Bo
心肌梗死(MI)是冠心病的一种限制性表型。到目前为止，一组基因和遗传位点与心肌梗死有关。然而，MI的遗传原因和潜在的分子机制在很大程度上仍不清楚。SIRT1是一种高度保守的NAD依赖的III类脱乙酰酶，参与了多种细胞过程，并与人类疾病有关。自噬是细胞主要的降解途径之一，在脂类代谢中起着重要作用。最近的研究表明，SIRT1去乙酰化了自噬相关基因，并且在MI患者中自噬基因的表达发生了变化。因此，我们假设SIRT1可能与心肌梗死的发病机制有关。在本研究中，对327例MI患者和358例对照组的SIRT1基因启动子进行了遗传分析。结果表明，共检测到6个单核苷酸多态和14个序列变异。在心肌梗塞患者中发现了5个新的杂合子变异(g.69643743Ins、g.69643840Ins、g.69643903G>；C、g.69644235G>；C和g.69644353G>；T)和一个单核苷酸多态(Rs35706870)。此外，还发现了5个新的杂合子突变(g.69643672G>；A，g.69644226C>；t.G.69644278A>；g.g.69644408G>；A和g.69644408G>；T)。其余的变异在心肌梗死患者和对照组中发现，频率相似。综上所述，在MI患者中发现的这些变异可能会改变SIRT1基因启动子的转录活性，从而改变SIRT1的水平，从而作为一个危险因素参与MI的发病。(C)2012 Elsevier Inc.保留所有权利。
Myocardial infarction (MI) is a restrictive phenotype of coronary artery disease. To date, a group of genes and genetic loci have been associated to MI. However, the genetic causes and underlying molecular mechanisms for MI remain largely unknown. SIRT1, one of highly conserved NAD-dependent class III deacetylases, has been involved in several cellular processes and implicated in human diseases. Autophagy is one of major cellular degradative pathways, which plays important roles in lipid metabolism. Recent studies have shown that SIRT1 deacetylates autophagy-related genes, and the expressions of autophagic genes are altered in MI patients. Accordingly, we hypothesized that SIRT1 may be linked to the MI pathogenesis. In this study, the SIRT1 gene promoter were genetically analyzed in large cohorts of MI patients (n = 327) and controls (n = 358). The results showed that six single-nucleotide polymorphisms and 14 sequence variants were identified. Among these, five novel heterozygous variants (g.69643743Ins, g.69643840Ins, g.69643903G > C, g.69644235G > C and g.69644353G > T) and one single-nucleotide polymorphism (rs35706870) were identified in MI patients, but in none of controls. Moreover, five novel heterozygous variants (g.69643672G > A, g.69644226C > T. g.69644278A > G. g.69644408G > A and g.69644408G > T) were only found in controls. The rest variants were found in MI patients and controls with similar frequencies. Taken together, the variants identified in MI patients may alter the transcriptional activities of SIRT1 gene promoter, which may change SIRT1 levels, contributing to the MI pathogenesis as a risk factor. (C) 2012 Elsevier Inc. All rights reserved.