BACKGROUND: Common genetic variations influence rejection, infection, drug metabolism, and side effect profiles after pediatric heart transplantation. Reports in adults suggest that genetic background may influence post-transplant renal function. In this multicenter study, we investigated the association of genetic polymorphisms (GPs) in a panel of candidate genes on renal function in 453 pediatric heart transplant recipients. METHODS: We performed genotyping for functional GPs in 19 candidate genes. Renal function was determined annually after transplantation by calculation of the estimated glomerular filtration rate (eGFR). Mixed-effects and Cox proportional hazard models were used to assess recipient characteristics and the effect of GPs on longitudinal eGFR and time to eGFR < 60 mL/min/1.73m(2). RESULTS: Mean age at transplantation was 6.2 ± 6.1 years. Mean follow-up was 5.1 ± 2.5 years. Older age at transplant and black race were independently associated with post-transplant renal dysfunction. Univariate analyses showed FASL (C-843T) T allele (p = 0.014) and HO-1 (A326G) G allele (p = 0.0017) were associated with decreased renal function. After adjusting for age and race, these associations were attenuated (FASL, p = 0.075; HO-1, p = 0.053). We found no associations of other GPs with post-transplant renal function, including GPs in TGFβ1, CYP3A5, ABCB1, and ACE. CONCLUSIONS: In this multicenter, large, sample of pediatric heart transplant recipients, we found no strong associations between GPs in 19 candidate genes and post-transplant renal function. Our findings contradict reported associations of CYP3A5 and TGFβ1 with renal function and suggest that genotyping for these GPs will not facilitate individualized immunosuppression for the purpose of protecting renal function after pediatric heart transplantation.
BACKGROUND: Common genetic variations influence rejection, infection, drug metabolism, and side effect profiles after pediatric heart transplantation. Reports in adults suggest that genetic background may influence post-transplant renal function. In this multicenter study, we investigated the association of genetic polymorphisms (GPs) in a panel of candidate genes on renal function in 453 pediatric heart transplant recipients. METHODS: We performed genotyping for functional GPs in 19 candidate genes. Renal function was determined annually after transplantation by calculation of the estimated glomerular filtration rate (eGFR). Mixed-effects and Cox proportional hazard models were used to assess recipient characteristics and the effect of GPs on longitudinal eGFR and time to eGFR < 60 mL/min/1.73m(2). RESULTS: Mean age at transplantation was 6.2 ± 6.1 years. Mean follow-up was 5.1 ± 2.5 years. Older age at transplant and black race were independently associated with post-transplant renal dysfunction. Univariate analyses showed FASL (C-843T) T allele (p = 0.014) and HO-1 (A326G) G allele (p = 0.0017) were associated with decreased renal function. After adjusting for age and race, these associations were attenuated (FASL, p = 0.075; HO-1, p = 0.053). We found no associations of other GPs with post-transplant renal function, including GPs in TGFβ1, CYP3A5, ABCB1, and ACE. CONCLUSIONS: In this multicenter, large, sample of pediatric heart transplant recipients, we found no strong associations between GPs in 19 candidate genes and post-transplant renal function. Our findings contradict reported associations of CYP3A5 and TGFβ1 with renal function and suggest that genotyping for these GPs will not facilitate individualized immunosuppression for the purpose of protecting renal function after pediatric heart transplantation.
Authors: Diana M Girnita; Maria M Brooks; Steven A Webber; Gilbert J Burckart; Robert Ferrell; Gina Zdanowicz; Susan DeCroo; Louise Smith; Richard Chinnock; Charles Canter; Linda Addonizio; Daniel Bernstein; James K Kirklin; Sarangarajan Ranganathan; David Naftel; Alin L Girnita; Adriana Zeevi Journal: Transplantation Date: 2008-06-15 Impact factor: 4.939
Authors: Daphne T Hsu; David C Naftel; Steven A Webber; William R Morrow; Charles E Canter; Richard E Chinnock; Mary Lynne Clark; James K Kirklin Journal: Congenit Heart Dis Date: 2006-05 Impact factor: 2.007
Authors: Jacqueline van de Wetering; Charlotte H E Weimar; Aggie H M M Balk; Joke I Roodnat; Cécile T J Holweg; Carla C Baan; Ron T van Domburg; Willem Weimar Journal: Transplantation Date: 2006-12-27 Impact factor: 4.939
Authors: Sylvie Di Filippo; Adriana Zeevi; Kevin K McDade; Gerard J Boyle; Susan A Miller; Sanjiv K Gandhi; Steven A Webber Journal: Hum Immunol Date: 2005-02 Impact factor: 2.850
Authors: Caroline K Lee; Laura L Christensen; John C Magee; Akinlolu O Ojo; William E Harmon; Nancy D Bridges Journal: J Heart Lung Transplant Date: 2007-05 Impact factor: 10.247