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

Haihua Wang1, Shufang Zhang2, Na Wang3

  • 1Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, Jining Medical University, 89 Guhuai Road, Jining, 272029, Shandong, China.

Human Genomics
|November 21, 2019
PubMed

Insights

Genetic variants in the Vascular Epithelial Growth Factor Receptor-1 (VEGFR-1) gene promoter were identified in patients with Acute Myocardial Infarction (AMI). These variants may impact VEGFR-1 gene activity, potentially contributing to AMI development.

Area of Science:

  • Cardiovascular Genetics
  • Molecular Biology
  • Disease Pathogenesis

Background:

  • Coronary artery disease (CAD), including acute myocardial infarction (AMI), is a complex condition driven by atherosclerosis.
  • Vascular Epithelial Growth Factor Receptor-1 (VEGFR-1) plays a role in angiogenesis and vascular permeability, and its absence leads to cardiac issues in mice.
  • VEGFR-1 gene variants are hypothesized to be involved in CAD due to observed cardiac dysfunction and fibrosis in related studies.

Purpose of the Study:

  • To investigate the potential role of VEGFR-1 gene variants in the development of AMI.
  • To genetically and functionally analyze the VEGFR-1 gene promoter in large cohorts of AMI patients and controls.

Main Methods:

  • Identification of DNA sequence variants (DSVs) and single-nucleotide polymorphisms (SNPs) in the VEGFR-1 gene promoter and 5'-untranslated region.
  • Functional analysis of identified variants using reporter gene assays in HEK-293 and H9c2 cells to assess transcriptional activity.
  • Electrophoretic mobility shift assays (EMSA) to evaluate the impact of variants on transcription factor binding.

Main Results:

  • Sixteen DNA sequence variants (DSVs), including six single-nucleotide polymorphisms (SNPs), were identified in the VEGFR-1 gene promoter and 5'-untranslated region.
  • Five novel DSVs and one SNP were exclusively found in the AMI patient group.
  • These variants significantly altered VEGFR-1 gene promoter transcriptional activity and affected transcription factor binding.

Conclusions:

  • Genetic variants within the VEGFR-1 gene promoter identified in AMI patients may influence its transcriptional activity.
  • These alterations in transcriptional activity could lead to changes in VEGFR-1 levels, potentially contributing to the pathogenesis of AMI.
Abstract

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