Abstract
BackgroundAcute myocardial infarction (AMI) is a severe type of coronary artery disease, caused by coronary occlusion and followed by cardiac ischaemia. GATA binding protein 5 (GATA5) is an important member of GATA family and plays an important role in vascular inflammation, endothelial function, oxidative stress and cell metabolism. Previous studies have shown that the DNA sequence variants (DSVs) in GATA4 and GATA6 promoter can increase susceptibility to AMI. In this study, we explored the relationship between GATA5 promoter and AMI for the first time, hoping to provide a new genetic basis for understanding the pathogenesis of AMI.MethodsGATA5 promoter was sequenced in 683 individuals (332 AMI patients and 351 controls). The transcriptional activity of the GATA5 promoter with or without DSVs in HEK-293 cells, H9c2 cells and primary neonatal rat cardiomyocytes were examined by Promega Dual-Luciferase® Reporter Assay system. Electrophoretic mobility shift assay (EMSA) was performed to explore whether the DSVs interfered with the binding of transcription factors (TFs).ResultsNine mutations have been found in GATA5 promoter, eight of them evidently altered the transcriptional activity of the GATA5 promoter, five of them disrupted the binding of TFs (such as farnesoid X receptor). Furthermore, haplotype AT (across rs80197101 and rs77067995) is a dangerous haplotype of AMI. Genotype GA and allele A of rs80197101 and genotype CT and allele T of rs77067995 are the risk factors of AMI.ConclusionsDSVs in GATA5 promoter can increase susceptibility to AMI. But the mechanism remains to be verified in vivo.
Highlights
Cardiovascular diseases (CVDs) are the leading cause of death globally [1]
Nine mutations have been found in GATA binding protein 5 (GATA5) promoter, eight of them altered the transcriptional activity of the GATA5 promoter, five of them disrupted the binding of transcription factors (TFs)
Quantitative data including age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), TG and total cholesterol (TC) was expressed as Mean±Standard Deviation
Summary
Acute myocardial infarction (AMI) is a serious type of CVDs, mainly related to coronary occlusion, accounting for more than 20% of cardiovascular deaths, and the 5-year survival rate of AMI is only 55% [2]. GATA binding protein 5 (GATA5) is a member of GATA family and plays an important role in CVDs as GATA5 loss-of-function mutations are closely related to congenital heart disease, atrial fibrillation, hypertension [5,6,7,8]. GATA binding protein 5 (GATA5) is an important member of GATA family and plays an important role in vascular inflammation, endothelial function, oxidative stress and cell metabolism. Previous studies have shown that the DNA sequence variants (DSVs) in GATA4 and GATA6 promoter can increase susceptibility to AMI. We explored the relationship between GATA5 promoter and AMI for the first time, hoping to provide a new genetic basis for understanding the pathogenesis of AMI
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