Impact of TGFbeta1 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 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.


CONCLUSIONS
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.
Departments of Pediatrics, Surgery, and Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. sylvie.di.filippo@wanadoo.fr
Sylvie
S
Di Filippo
Adriana
A
Zeevi
Kevin K
KK
McDade
Olivier
O
Bastien
Steven A
SA
Webber
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003327:Coronary Disease / Q000235:genetics; D005260:Female; D006084:Graft Rejection / Q000235:genetics*; D016027:Heart Transplantation / Q000276:immunology; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D014184:Transplantation, Homologous
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1