Functional Genetic Variant in ATG5 Gene Promoter in Acute Myocardial Infarction
Coronary artery disease (CAD) including acute myocardial infarction (AMI) is an inflammatory and metabolic disease mainly caused by atherosclerosis. Dysfunctional autophagy has been associated with abnormal lipid metabolism and inflammation. In previous studies, we have reported altered autophagic a...
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Wiley
2020-01-01
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| Series: | Cardiology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2020/9898301 |
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| author | Yexin Zhang Xiaohui He Jiarui Li Wentao Yang Yinghua Cui Shuchao Pang Haihua Wang Bo Yan |
| author_facet | Yexin Zhang Xiaohui He Jiarui Li Wentao Yang Yinghua Cui Shuchao Pang Haihua Wang Bo Yan |
| author_sort | Yexin Zhang |
| collection | DOAJ |
| description | Coronary artery disease (CAD) including acute myocardial infarction (AMI) is an inflammatory and metabolic disease mainly caused by atherosclerosis. Dysfunctional autophagy has been associated with abnormal lipid metabolism and inflammation. In previous studies, we have reported altered autophagic activity in AMI patients. As autophagy-related protein 5 (ATG5) is a core protein in autophagy, we speculated that altered ATG5 level may contribute to CAD and AMI development. In this study, the promoter of the ATG5 gene was genetically and functionally investigated in large groups of AMI patients (n = 378) and ethnic-matched healthy controls (n = 386). The results showed that a total of 15 genetic variants including 6 single-nucleotide polymorphisms (SNPs) in the ATG5 gene promoter were found in this study population. A novel deletion variant (g.106326168_70delTCT) and an SNP [g.106325757C > G (rs190825454)] were found in one 66-year-old male patient with non-ST-segment elevated AMI, but in none of controls. In cultured HEK-293 and H9c2 cells, the deletion variant significantly decreased the transcriptional activity of the ATG5 gene promoter (P<0.01). In contrast, the genetic variants either identified only in controls or found in both AMI patients and controls did not affect the transcriptional activity of the ATG5 gene promoter (P>0.05). Furthermore, an electrophoretic mobility shift assay showed that the deletion variant evidently affected the binding of a transcription factor. Therefore, the genetic variant identified in AMI may affect the activity of the ATG5 gene promoter and change the ATG5 level, contributing to AMI as a rare risk factor. |
| format | Article |
| id | doaj-art-8ff0e92e030343c58da31dd13157d418 |
| institution | Kabale University |
| issn | 2090-8016 2090-0597 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cardiology Research and Practice |
| spelling | doaj-art-8ff0e92e030343c58da31dd13157d4182025-02-03T05:52:44ZengWileyCardiology Research and Practice2090-80162090-05972020-01-01202010.1155/2020/98983019898301Functional Genetic Variant in ATG5 Gene Promoter in Acute Myocardial InfarctionYexin Zhang0Xiaohui He1Jiarui Li2Wentao Yang3Yinghua Cui4Shuchao Pang5Haihua Wang6Bo Yan7Department of Medicine, Shandong University School of Medicine, Jinan, Shandong 250012, ChinaDepartment of Medicine, Shandong University School of Medicine, Jinan, Shandong 250012, ChinaDepartment of Medicine, Shandong University School of Medicine, Jinan, Shandong 250012, ChinaDepartment of Medicine, Shandong University School of Medicine, Jinan, Shandong 250012, ChinaDivision of Cardiology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, ChinaShandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, ChinaShandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, ChinaShandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, ChinaCoronary artery disease (CAD) including acute myocardial infarction (AMI) is an inflammatory and metabolic disease mainly caused by atherosclerosis. Dysfunctional autophagy has been associated with abnormal lipid metabolism and inflammation. In previous studies, we have reported altered autophagic activity in AMI patients. As autophagy-related protein 5 (ATG5) is a core protein in autophagy, we speculated that altered ATG5 level may contribute to CAD and AMI development. In this study, the promoter of the ATG5 gene was genetically and functionally investigated in large groups of AMI patients (n = 378) and ethnic-matched healthy controls (n = 386). The results showed that a total of 15 genetic variants including 6 single-nucleotide polymorphisms (SNPs) in the ATG5 gene promoter were found in this study population. A novel deletion variant (g.106326168_70delTCT) and an SNP [g.106325757C > G (rs190825454)] were found in one 66-year-old male patient with non-ST-segment elevated AMI, but in none of controls. In cultured HEK-293 and H9c2 cells, the deletion variant significantly decreased the transcriptional activity of the ATG5 gene promoter (P<0.01). In contrast, the genetic variants either identified only in controls or found in both AMI patients and controls did not affect the transcriptional activity of the ATG5 gene promoter (P>0.05). Furthermore, an electrophoretic mobility shift assay showed that the deletion variant evidently affected the binding of a transcription factor. Therefore, the genetic variant identified in AMI may affect the activity of the ATG5 gene promoter and change the ATG5 level, contributing to AMI as a rare risk factor.http://dx.doi.org/10.1155/2020/9898301 |
| spellingShingle | Yexin Zhang Xiaohui He Jiarui Li Wentao Yang Yinghua Cui Shuchao Pang Haihua Wang Bo Yan Functional Genetic Variant in ATG5 Gene Promoter in Acute Myocardial Infarction Cardiology Research and Practice |
| title | Functional Genetic Variant in ATG5 Gene Promoter in Acute Myocardial Infarction |
| title_full | Functional Genetic Variant in ATG5 Gene Promoter in Acute Myocardial Infarction |
| title_fullStr | Functional Genetic Variant in ATG5 Gene Promoter in Acute Myocardial Infarction |
| title_full_unstemmed | Functional Genetic Variant in ATG5 Gene Promoter in Acute Myocardial Infarction |
| title_short | Functional Genetic Variant in ATG5 Gene Promoter in Acute Myocardial Infarction |
| title_sort | functional genetic variant in atg5 gene promoter in acute myocardial infarction |
| url | http://dx.doi.org/10.1155/2020/9898301 |
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