Impact of TGF??1 Gene Polymorphisms on Acute and Chronic Rejection in Pediatric Heart Transplant Allografts:

Background. The aim of this study was to assess the influence of IL-10 and TGF beta 1 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. Corollary artery disease (CAD) was diagnosed by angiography or on macroscopic examination. Genotyping PCR-SSP were performed for IL-10 and TGF beta 1 (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. TGF beta 1-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). TGF beta 1-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). TGF beta 1-codon10 gene polymorphisms were not associated with CAD. Conclusion. IL-10 low-producers have an increased risk of acute rejection. High-expressors of TGF beta 1-codon 10-25 have an increased risk of acute rejection and CAD, while TGF beta 1-codon25 high-production is associated with coronary disease. Genetic polymorphism may reveal patients at high-risk in whom therapies and monitoring should be adjusted.