Identification and functional analysis of genetic variants in TBX5 gene promoter in patients with acute myocardial infarction
Abstract Background Coronary artery disease (CAD), including acute myocardial infarction (AMI), is a common complex disease. Although a great number of genetic loci and variants for CAD have been identified, genetic causes and underlying mechanisms remain largely unclear. Epidemiological studies hav...
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| Format: | Article |
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BMC
2019-11-01
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| Series: | BMC Cardiovascular Disorders |
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| Online Access: | http://link.springer.com/article/10.1186/s12872-019-1237-6 |
| _version_ | 1818299667761332224 |
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| author | Shuai Wang Jie Zhang Xiaohui He Yexin Zhang Jing Chen Qiang Su Shuchao Pang Shufang Zhang Yinghua Cui Bo Yan |
| author_facet | Shuai Wang Jie Zhang Xiaohui He Yexin Zhang Jing Chen Qiang Su Shuchao Pang Shufang Zhang Yinghua Cui Bo Yan |
| author_sort | Shuai Wang |
| collection | DOAJ |
| description | Abstract Background Coronary artery disease (CAD), including acute myocardial infarction (AMI), is a common complex disease. Although a great number of genetic loci and variants for CAD have been identified, genetic causes and underlying mechanisms remain largely unclear. Epidemiological studies have revealed that CAD incidence is strikingly higher in patients with congenital heart disease than that in normal population. T-box transcription factors play critical roles in embryonic development. In particular, TBX5 as a dosage-sensitive regulator is required for cardiac development and function. Thus, dysregulated TBX5 gene expression may be involved in CAD development. Methods TBX5 gene promoter was genetically and functionally analysed in large groups of AMI patients (n = 432) and ethnic-matched healthy controls (n = 448). Results Six novel heterozygous DNA sequence variants (DSVs) in the TBX5 gene promoter (g.4100A > G, g.4194G > A, g.4260 T > C, g.4367C > A, g.4581A > G and g.5004G > T) were found in AMI patients, but in none of controls. These DSVs significantly changed the activity of TBX5 gene promoter in cultured cells (P < 0.05). Furthermore, three of the DSVs (g.4100A > G, g.4260 T > C and g.4581A > G) evidently modified the binding sites of unknown transcription factors. Conclusions The DSVs identified in AMI patients may alter TBX5 gene promoter activity and change TBX5 level, contributing to AMI development as a rare risk factor. |
| first_indexed | 2024-12-13T04:54:52Z |
| format | Article |
| id | doaj.art-484ecb4c0a324587991b1de13b56c420 |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-12-13T04:54:52Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-484ecb4c0a324587991b1de13b56c4202022-12-21T23:58:55ZengBMCBMC Cardiovascular Disorders1471-22612019-11-011911810.1186/s12872-019-1237-6Identification and functional analysis of genetic variants in TBX5 gene promoter in patients with acute myocardial infarctionShuai Wang0Jie Zhang1Xiaohui He2Yexin Zhang3Jing Chen4Qiang Su5Shuchao Pang6Shufang Zhang7Yinghua Cui8Bo Yan9Department of Medicine, Shandong University School of MedicineDepartment of Medicine, Shandong University School of MedicineDepartment of Medicine, Shandong University School of MedicineDepartment of Medicine, Shandong University School of MedicineDepartment of Medicine, Shandong University School of MedicineDepartment of Medicine, Shandong University School of MedicineShandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, Jining Medical UniversityDivision of Cardiology, Affiliated Hospital of Jining Medical University, Jining Medical UniversityDivision of Cardiology, Affiliated Hospital of Jining Medical University, Jining Medical UniversityShandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, Jining Medical UniversityAbstract Background Coronary artery disease (CAD), including acute myocardial infarction (AMI), is a common complex disease. Although a great number of genetic loci and variants for CAD have been identified, genetic causes and underlying mechanisms remain largely unclear. Epidemiological studies have revealed that CAD incidence is strikingly higher in patients with congenital heart disease than that in normal population. T-box transcription factors play critical roles in embryonic development. In particular, TBX5 as a dosage-sensitive regulator is required for cardiac development and function. Thus, dysregulated TBX5 gene expression may be involved in CAD development. Methods TBX5 gene promoter was genetically and functionally analysed in large groups of AMI patients (n = 432) and ethnic-matched healthy controls (n = 448). Results Six novel heterozygous DNA sequence variants (DSVs) in the TBX5 gene promoter (g.4100A > G, g.4194G > A, g.4260 T > C, g.4367C > A, g.4581A > G and g.5004G > T) were found in AMI patients, but in none of controls. These DSVs significantly changed the activity of TBX5 gene promoter in cultured cells (P < 0.05). Furthermore, three of the DSVs (g.4100A > G, g.4260 T > C and g.4581A > G) evidently modified the binding sites of unknown transcription factors. Conclusions The DSVs identified in AMI patients may alter TBX5 gene promoter activity and change TBX5 level, contributing to AMI development as a rare risk factor.http://link.springer.com/article/10.1186/s12872-019-1237-6Acute myocardial infarctionTBX5Gene expression regulationPromoterGenetic variants |
| spellingShingle | Shuai Wang Jie Zhang Xiaohui He Yexin Zhang Jing Chen Qiang Su Shuchao Pang Shufang Zhang Yinghua Cui Bo Yan Identification and functional analysis of genetic variants in TBX5 gene promoter in patients with acute myocardial infarction BMC Cardiovascular Disorders Acute myocardial infarction TBX5 Gene expression regulation Promoter Genetic variants |
| title | Identification and functional analysis of genetic variants in TBX5 gene promoter in patients with acute myocardial infarction |
| title_full | Identification and functional analysis of genetic variants in TBX5 gene promoter in patients with acute myocardial infarction |
| title_fullStr | Identification and functional analysis of genetic variants in TBX5 gene promoter in patients with acute myocardial infarction |
| title_full_unstemmed | Identification and functional analysis of genetic variants in TBX5 gene promoter in patients with acute myocardial infarction |
| title_short | Identification and functional analysis of genetic variants in TBX5 gene promoter in patients with acute myocardial infarction |
| title_sort | identification and functional analysis of genetic variants in tbx5 gene promoter in patients with acute myocardial infarction |
| topic | Acute myocardial infarction TBX5 Gene expression regulation Promoter Genetic variants |
| url | http://link.springer.com/article/10.1186/s12872-019-1237-6 |
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