Genetic Polymorphism in Platelet-derived Growth Factor and Vascular Endothelial Growth Factor Are Significantly Associated With Cardiac Allograft Vasculopathy

Anat Roitberg-Tambur*, Salpy Pamboukian, Maria Rosa Costanzo, Alain Heroux

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Background: The role of cytokine gene polymorphism and its association with acute heart allograft rejection and cardiac allograft vasculopathy (CAV) is controversial. The role of growth factor gene polymorphism has never been investigated in heart allograft recipients. Methods: Seventy heart transplant recipients were studied. Mean age at transplant was 50.4 ± 12.4 years (73% white, 91% male). Patients were followed for an average of 28 ± 12 months. Cellular rejection episodes were determined based on criteria established by the International Society of Heart and Lung Transplantation. Angiography and intravascular ultrasound (IVUS) were performed annually. Cytokine and growth factor polymorphism data were analyzed using the single-nucleotide polymorphism polymerase chain reaction (SNP PCR) approach. Results: Patients who developed early CAV, documented by angiography, had increased frequency of the interferon-γ high-producer phenotype, increased frequency of PDGF -286 AA, and decreased frequency of PDGF -1135 CC (p < 0.03, p < 0.03 and p = 0.01, respectively). Platelet-derived growth factor (PDGF) associations with early CAV were substantiated when vasculopathy was determined by IVUS. Additional associations were identified with vascular endothelial growth factor (VEGF) polymorphisms -1154 GG and -2578 AC (p < 0.03 and p = 0.01, respectively). Some of these associations translated to decreased patient survival, as indicated by Kaplan-Meier analysis. No significant association was identified between cytokine gene polymorphism (tumor necrosis factor-α, transforming growth factor-β, interferon-γ, interleukin-6 and interleukin-10) and acute cellular rejection episodes. Conclusions: These data suggest an association between PDGF and VEGF polymorphism and CAV. It is essential, however, due to the redundancy of the immune system and other confounding factors, that future studies be centrally conducted and include multiple programs, large cohorts of patients and properly chosen controls. Only then will we be able to identify the true association between cytokine and growth factor polymorphism and heart transplant outcome.

Original languageEnglish (US)
Pages (from-to)690-698
Number of pages9
JournalJournal of Heart and Lung Transplantation
Volume25
Issue number6
DOIs
StatePublished - Jun 1 2006

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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