Impact of TGFbeta1 gene polymorphisms on acute and chronic rejection in pediatric heart transplant allografts

Transplantation. 2006 Mar 27;81(6):934-9. doi: 10.1097/01.tp.0000202725.55923.37.

Abstract

Background: The aim of this study was to assess the influence of IL-10 and TGFbeta1 gene polymorphisms on the development of acute rejection and coronary disease in pediatric heart transplant recipients.

Methods: Patients were classified as either Rejectors or Nonrejectors. Coronary artery disease (CAD) was diagnosed by angiography or on macroscopic examination. Genotyping PCR-SSP were performed for IL-10 and TGFbeta1 (codon 10 and 25) in 111 patients. Thirty-nine were Rejectors and 31 developed CAD.

Results: The proportion of IL-10 low-producers was higher in Rejectors than in Nonrejectors (respectively 46% versus 22%, P=0.009). IL-10 gene polymorphism was not associated with CAD. TGFbeta1-codon10-25 high-producers were 92.3% in Rejectors and 75% in Nonrejectors (P=0.026), 93.5% in patients with CAD and 76.2% in patients free from CAD (P=0.037). TGFbeta1-codon25 high-production separately analyzed correlated with CAD (31/31 high-producers in CAD=100% versus 69/80 in noCAD patients=86.2%, P=0.03). TGFbeta1-codon10 gene polymorphisms were not associated with CAD.

Conclusion: IL-10 low-producers have an increased risk of acute rejection. High-expressors of TGFbeta1-codon10-25 have an increased risk of acute rejection and CAD, while TGFbeta1-codon25 high-production is associated with coronary disease. Genetic polymorphism may reveal patients at high-risk in whom therapies and monitoring should be adjusted.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Coronary Disease / genetics
  • Female
  • Graft Rejection / genetics*
  • Heart Transplantation* / immunology
  • Humans
  • Male
  • Polymorphism, Genetic*
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta1
  • Transplantation, Homologous

Substances

  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1