The Influence of Race and Common Genetic Variations on Outcomes After Pediatric Heart Transplantation |
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Authors: | D. J. Green M. M. Brooks G. J. Burckart R. E. Chinnock C. Canter L. J. Addonizio D. Bernstein J. K. Kirklin D. C. Naftel D. M. Girnita A. Zeevi S. A. Webber |
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Affiliation: | 1. Pediatric Clinical Pharmacology Staff, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD;2. Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA;3. Department of Pediatrics, Loma Linda University, Loma Linda, CA;4. Division of Cardiology, Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO;5. Division of Cardiology, Department of Pediatrics, Columbia University, New York, NY;6. Division of Cardiology, Department of Pediatrics, Stanford University, Lucile Packard Children's Hospital, Palo Alto, CA;7. Department of Surgery, University of Alabama at Birmingham, Birmingham, AL;8. Department of Pathology, Thomas E Starzl Transplant Institute, University of Pittsburgh, Pittsburgh, PA;9. Department of Pediatrics, Vanderbilt University, Nashville, TN |
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Abstract: | Significant racial disparity remains in the incidence of unfavorable outcomes following heart transplantation. We sought to determine which pediatric posttransplantation outcomes differ by race and whether these can be explained by recipient demographic, clinical, and genetic attributes. Data were collected for 80 black and 450 nonblack pediatric recipients transplanted at 1 of 6 centers between 1993 and 2008. Genotyping was performed for 20 candidate genes. Average follow‐up was 6.25 years. Unadjusted 5‐year rates for death (p = 0.001), graft loss (p = 0.015), acute rejection with severe hemodynamic compromise (p = 0.001), late rejection (p = 0.005), and late rejection with hemodynamic compromise (p = 0.004) were significantly higher among blacks compared with nonblacks. Black recipients were more likely to be older at the time of transplantation (p < 0.001), suffer from cardiomyopathy (p = 0.004), and have public insurance (p < 0.001), and were less likely to undergo induction therapy (p = 0.0039). In multivariate regression models adjusting for age, sex, cardiac diagnosis, insurance status, and genetic variations, black race remained a significant risk factor for all the above outcomes. These clinical and genetic variables explained only 8–19% of the excess risk observed for black recipients. We have confirmed racial differences in survival, graft loss, and several rejection outcomes following heart transplantation in children, which could not be fully explained by differences in recipient attributes. |
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Keywords: | clinical research/practice health services and outcomes research pediatrics heart transplantation/cardiology genetics disparities ethnicity/race genetics patient characteristics |
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