Sequence Variants of SIRT6 Gene Promoter in Myocardial Infarction
Sequence Variants of SIRT6 Gene Promoter in Myocardial Infarction
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心肌梗死SIRT6基因启动子序列变异
DOI：
10.1089/gtmb.2015.0188
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发表时间：
2016
影响因子：
1.4
通讯作者：
Yan Bo
中科院分区：
文献类型：
--
作者：
Wang Lekun;Ma Ling;Pang Shuchao;Huang Jian;Yan Bo
目的冠状动脉疾病（Coronary artery disease，CAD）包括心肌梗死（myocardial infarction，MI），是一种常见的由动脉粥样硬化引起的复杂疾病.尽管有超过50种遗传变异与CAD相关，但这些基因座总共仅占CAD病例的10%。低频率和罕见频率的遗传变异已被认为是CAD的主要原因。SIRT6是一种高度保守的NAD依赖性III类脱乙酰酶，与心血管疾病有关。考虑到SIRT6在心血管系统、炎症、脂质和胆固醇代谢中发挥的重要作用，遗传变异被假设为有助于MI的发展。包括七个单核苷酸多态性（SNPs）。两个新的杂合子DSV，g.4183823G>C和g.4183742G>A，在两个MI患者中被鉴定，但在对照组中没有。两个SNPs，g.4183685T>C（rs4359565）和g.4182942C>A（rs3760905），被发现在MI患者与显着较高的频率与controls.ConclusionsThese DSV确定MI患者可能会改变SIRT6基因启动子的转录活性和改变SIRT6水平，这可能有助于MI的风险。
AimsCoronary artery disease (CAD), including myocardial infarction (MI), is a common complex disease caused by atherosclerosis. Although more than 50 genetic variants have been associated with CAD, these loci collectively account for only 10% of CAD cases. Genetic variants of low and rare frequencies have been proposed as the main causes of CAD. SIRT6, one of the highly conserved NAD-dependent class III deacetylases, has been implicated in cardiovascular diseases. Considering the important roles that SIRT6 plays in the cardiovascular system, inflammation, and lipid and cholesterol metabolism, genetic variants were hypothesized to contribute to MI development.MethodsThe promoter regions of theSIRT6gene were genetically analyzed in large cohorts of MI patients (n= 371) and ethnically-matched controls (n= 383).ResultsA total of 15 DNA sequence variants (DSVs) were identified, including seven single-nucleotide polymorphisms (SNPs). Two novel heterozygous DSVs, g.4183823G>C and g.4183742G>A, were identified in two MI patients but in none of the controls. Two SNPs, g.4183685T>C (rs4359565) and g.4182942C>A (rs3760905), were found in MI patients with significantly higher frequencies compared with controls.ConclusionsThese DSVs identified in MI patients may alter the transcriptional activity of theSIRT6gene promoter and alter SIRT6 levels which might contribute to the risk of MI.