Genetic variants of VEGFR-1 gene promoter in acute myocardial infarction

Haihua Wang,Shufang Zhang,Jie Zhang,Shuchao Pang,Yinghua Cui,Xiaohui He,Bo Yan,Na Wang,Mingkai Chen

doi:10.1186/s40246-019-0243-1

Abstract

BackgroundCoronary artery disease (CAD) including acute myocardial infarction (AMI) is a common complex disease caused by atherosclerosis. Vascular epithelial growth factor receptor-1 (VEGFR-1) stimulates angiogenesis and vascular permeability, and functions as a decoy to sequester VEGF and prevent initiation of intracellular signaling. VEGFR-1 knockout mice exhibit significantly higher mortality due to heart failure, cardiac hypertrophy, and cardiac dysfunction. An evident increase in macrophage infiltration and cardiac fibrosis are also observed after transverse aortic constriction. Therefore, VEGFR-1 gene variants may be involved in CAD. In this study, VEGFR-1 gene promoter was genetically and functionally analyzed in large cohorts of AMI patients and ethnic-matched controls.ResultsA total of 16 DNA sequence variants (DSVs) including six single-nucleotide polymorphisms (SNPs) were found in the VEGFR-1 gene promoter and 5′-untranslated region. Five novel DSVs and one SNP were only identified in AMI patients group. These DSVs and SNP significantly altered the transcriptional activity of the VEGFR-1 gene promoter in both HEK-293 and H9c2 cells (P < 0.05). Further electrophoretic mobility shift assay indicated that the DSVs and SNPs evidently affected the binding of transcription factors.ConclusionsThe genetic variants in VEGFR-1 gene identified in AMI patients may alter the transcriptional activity of the VEGFR-1 gene promoter and change VEGFR-1 level, contributing to AMI development.

Highlights

Coronary artery disease (CAD) including acute myocardial infarction (AMI) is a common complex disease caused by atherosclerosis
Genetic variants identified in the Vascular epithelial growth factor receptor-1 (VEGFR-1) gene promoter and 5′-UTR In this study population, a total of 16 DNA sequence variants (DSVs) were identified in the VEGFR-1gene promoter and 5′-untranlated region (5′-UTR), including ten novel heterozygous DSVs and six single-nucleotide polymorphisms (SNPs)
The results showed that genetic variants found only in AMI patients or healthy controls may abolish or create binding sites for transcription factors

Summary

Introduction

Coronary artery disease (CAD) including acute myocardial infarction (AMI) is a common complex disease caused by atherosclerosis. VEGFR-1 gene promoter was genetically and functionally analyzed in large cohorts of AMI patients and ethnic-matched controls. Coronary artery disease (CAD) including acute myocardial infarction (AMI) is a common complex disease, which is mainly caused by atherosclerosis, an inflammatory and metabolic disease. Genetic variants of low and rare frequencies have been proposed to contribute to CAD and AMI. Proper development of the coronary vascular system is critical to deliver blood supply for myocardial growth and to ensure efficient cardiac contraction [7]. Vascular endothelial growth factor receptor-1 (VEGFR-1) is a transmembrane

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