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THE IMPACT OF GROWTH FACTOR GENE POLYMORPHISM ON THE DEVELOPMENT OF CORONARY ARTERY DISEASE AND IMPAIRED RENAL FUNCTION IN PEDIATRIC HEART TRANSPLANTATION.
Adriana Zeevi, PhD, Sylvie Di Filippo, MD, Anat Tambur, PhD, Gilbert Burckart, PhD, Kevin McDade, BS, Susan Miller, MD and Steven Webber, MD. Pittsburgh PA, USA, UPMC, Pathology; Chicago IL, Rush Medical Center, Pathology; UPMC Cardiology and Los Angeles CA, University of South California, Pharmacy.

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In this study we assessed the influence of IL-10 and growth factors TGFβ1, VEGF, PDGF gene polymorphism on the development of coronary artery disease (CAD) and renal dysfunction in pediatric heart transplant recipients.
Patients were classified as rejectors (Rej) if they had refractory acute rejection and non –rejectors otherwise. Renal function was assessed by Schwarz formula-calculated Creatinine Clearance (CrCl ml/mn/1.73m2), pre-transplant (pre-Tx), at 1 month, 6 months, 1 year and yearly up to 7 years. Impaired renal function was defined as CrCl less than 80ml/mn/1.73m2. Genotyping using PCR specific primers were performed for the following IL-10, TGFβ1 (codon 10 and 25) in 111 patients and VEGF (-2578A/C), PDGF (+1135 A/C) in 80 patients.
The proportion of IL-10 Low producers was higher in Rej than NRej (46% versus 22%, p=0.009) but had no association with CAD. TGFβ1 High producers was higher in Rej than in NRej( 92% vs. 75% p=0.026) and in patients with CAD (93% vs. 76% , p=0.037). Allele AA for VEGF was associated with acute rejection but not with CAD (34.5% Rej vs. 15.7% NRej). PDGF polymorphism was not associated with either acute or chronic rejection. TGFβ1 High producers had worse renal function than Int/Low producers at every post-Tx time period (1-year CrCl 92±38 vs 113±30,p=0.03) and was more frequent in patients with post-Tx CrCl<80 ( 94% vs 68%, p=0.004).
Conclusion: This study shows that TGFβ1 is associated with both higher frequency of CAD and renal dysfunction in pediatric heart Tx recipients.