Functional variants of the ATG7 gene promoter in acute myocardial infarction.
Functional variants of the ATG7 gene promoter in acute myocardial infarction.
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ATG7基因启动子在急性心肌梗死中的功能变异
DOI：
10.1002/mgg3.508
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发表时间：
2018-11
影响因子：
2
通讯作者：
Yan B
中科院分区：
文献类型：
--
作者：
Zhang P;Zhang J;Zhang Y;Wang S;Pang S;Yan B
包括急性心肌梗死（AMI）在内的冠状动脉疾病主要由动脉粥样硬化（atherosclerosis）引起，是一种炎症和代谢性疾病。自噬已被证明在脂质代谢和炎症中起关键作用。在AMI患者中已经报道了改变的自噬活性。然而，AMI中功能障碍性自噬的分子基础仍然无法解释。在这项研究中，在AMI患者（n = 355）和种族匹配的健康对照（n = 363）的大队列中，对编码自噬核心蛋白的ATG 7基因的启动子进行了遗传和功能分析。并探讨了相关的分子机制。在ATG 7基因启动子中共发现了19种DNA序列变异（DSV），包括单核苷酸多态性（SNP）。仅在AMI患者组中发现了2个新的DSV和5个SNPs。这些DSV和SNP（除了一个SNP）显著改变了HEK-293和H9 c2细胞中ATG 7基因启动子的转录活性（p < 0.05）。进一步的电泳迁移率变动分析表明，DSV和SNPs明显影响转录因子的结合。 在AMI患者中发现的ATG 7基因DSV和SNPs可能改变ATG 7基因启动子的转录活性并改变ATG 7水平，作为一种罕见的危险因素促进AMI的发展。
Coronary artery disease including acute myocardial infarction (AMI) is mainly caused by atherosclerosis, an inflammatory and metabolic disease. Autophagy has been demonstrated to play critical roles in lipid metabolism and inflammation. Altered autophagic activity has been reported in AMI patients. However, molecular basis for dysfunctional autophagy in AMI remains unexplained. In this study, the promoter of the ATG7 gene, encoding a core protein for autophagy, was genetically and functionally analyzed in large cohorts of AMI patients (n = 355) and ethnic‐matched healthy controls (n = 363). Related molecular mechanisms were also explored. A total of 19 DNA sequence variants (DSVs) including single‐nucleotide polymorphisms (SNPs) were found in the ATG7 gene promoter. Two novel DSVs and five SNPs were only identified in AMI patients group. These DSVs and SNPs, except one SNP, significantly altered the transcriptional activity of the ATG7 gene promoter in both HEK‐293 and H9c2 cells (p < 0.05). Further electrophoretic mobility shift assay revealed that the DSVs and SNPs evidently affected the binding of transcription factors. ATG7 gene DSVs and SNPs identified in AMI patients may alter the transcriptional activity of the ATG7 gene promoter and change ATG7 level, contributing to the AMI development as a rare risk factor.
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期刊：
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通讯作者：
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