TY - JOUR
T1 - Renal function and genetic polymorphisms in pediatric heart transplant recipients
AU - Feingold, Brian
AU - Brooks, Maria M.
AU - Zeevi, Adriana
AU - Ohmann, Erin L.
AU - Burckart, Gilbert J.
AU - Ferrell, Robert E.
AU - Chinnock, Richard
AU - Canter, Charles
AU - Addonizio, Linda
AU - Bernstein, Daniel
AU - Kirklin, James K.
AU - Naftel, David C.
AU - Webber, Steven A.
N1 - Funding Information:
Dr. Feingold's effort on this project was supported by the National Institutes of Health through Grants KL2 RR-024154 and KL2 TR-000146 . This project was also supported by the National Heart Lung Blood Institute, National Institutes of Health ( 5P50 HL 07432-05 ). The content is solely the responsibility of the authors and does not necessarily represent the views of the National Heart Lung Blood Institute or the National Institutes of Health.
PY - 2012/9
Y1 - 2012/9
N2 - 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/1.73m2. 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.
AB - 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/1.73m2. 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.
KW - TGF-beta1
KW - cytochrome P450
KW - genetic polymorphism
KW - heart transplantation
KW - pediatrics
KW - renal function
UR - http://www.scopus.com/inward/record.url?scp=84864944603&partnerID=8YFLogxK
U2 - 10.1016/j.healun.2012.05.010
DO - 10.1016/j.healun.2012.05.010
M3 - Article
C2 - 22789135
AN - SCOPUS:84864944603
SN - 1053-2498
VL - 31
SP - 1003
EP - 1008
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 9
ER -