Renal function and genetic polymorphisms in pediatric heart transplant recipients

Brian Feingold, Maria M. Brooks, Adriana Zeevi, Erin L. Ohmann, Gilbert J. Burckart, Robert E. Ferrell, Richard Chinnock, Charles Canter, Linda Addonizio, Daniel Bernstein, James K. Kirklin, David C. Naftel, Steven A. Webber

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5 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1003-1008
Number of pages6
JournalJournal of Heart and Lung Transplantation
Volume31
Issue number9
DOIs
StatePublished - Sep 1 2012

Keywords

  • TGF-beta1
  • cytochrome P450
  • genetic polymorphism
  • heart transplantation
  • pediatrics
  • renal function

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    Feingold, B., Brooks, M. M., Zeevi, A., Ohmann, E. L., Burckart, G. J., Ferrell, R. E., Chinnock, R., Canter, C., Addonizio, L., Bernstein, D., Kirklin, J. K., Naftel, D. C., & Webber, S. A. (2012). Renal function and genetic polymorphisms in pediatric heart transplant recipients. Journal of Heart and Lung Transplantation, 31(9), 1003-1008. https://doi.org/10.1016/j.healun.2012.05.010