The Relationships between Polymorphisms in Genes Encoding the Growth Factors TGF-β1, PDGFB, EGF, bFGF and VEGF-A and the Restenosis Process in Patients with Stable Coronary Artery Disease Treated with Bare Metal Stent

PLoS One. 2016 Mar 1;11(3):e0150500. doi: 10.1371/journal.pone.0150500. eCollection 2016.

Abstract

Background: Neointima forming after stent implantation consists of vascular smooth muscle cells (VSMCs) in 90%. Growth factors TGF-β1, PDGFB, EGF, bFGF and VEGF-A play an important role in VSMC proliferation and migration to the tunica intima after arterial wall injury. The aim of this paper was an analysis of functional polymorphisms in genes encoding TGF-β1, PDGFB, EGF, bFGF and VEGF-A in relation to in-stent restenosis (ISR).

Materials and methods: 265 patients with a stable coronary artery disease (SCAD) hospitalized in our center in the years 2007-2011 were included in the study. All patients underwent stent implantation at admission to the hospital and had another coronary angiography performed due to recurrence of the ailments or a positive result of the test assessing the coronary flow reserve. Angiographically significant ISR was defined as stenosis >50% in the stented coronary artery segment. The patients were divided into two groups-with angiographically significant ISR (n = 53) and without significant ISR (n = 212). Additionally, the assessment of late lumen loss (LLL) in vessel was performed. EGF rs4444903 polymorphism was genotyped using the PCR-RFLP method whilst rs1800470 (TGFB1), rs2285094 (PDGFB) rs308395 (bFGF) and rs699947 (VEGF-A) were determined using the TaqMan method.

Results: Angiographically significant ISR was significantly less frequently observed in the group of patients with the A/A genotype of rs1800470 polymorphism (TGFB1) versus patients with A/G and G/G genotypes. In the multivariable analysis, LLL was significantly lower in patients with the A/A genotype of rs1800470 (TGFB1) versus those with the A/G and G/G genotypes and higher in patients with the A/A genotype of the VEGF-A polymorphism versus the A/C and C/C genotypes. The C/C genotype of rs2285094 (PDGFB) was associated with greater LLL compared to C/T heterozygotes and T/T homozygotes.

Conclusions: The polymorphisms rs1800470, rs2285094 and rs6999447 of the TGFB1, PDGFB and VEGF-A genes, respectively, are associated with LLL in patients with SCAD treated by PCI with a metal stent implantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / surgery
  • Coronary Restenosis / genetics*
  • Epidermal Growth Factor / genetics*
  • Epidermal Growth Factor / physiology
  • Female
  • Fibroblast Growth Factor 2 / genetics*
  • Fibroblast Growth Factor 2 / physiology
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Polymorphism, Single Nucleotide / physiology
  • Proto-Oncogene Proteins c-sis / genetics*
  • Proto-Oncogene Proteins c-sis / physiology
  • Stents* / adverse effects
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / physiology
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / physiology

Substances

  • Proto-Oncogene Proteins c-sis
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor

Grants and funding

The study was financed by the National Science Centre (NCN), Poland (2011/01/D/NZ5/04387; 2014/13/B/NZ5/03166). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.