The Influence of Race and Common Genetic Variations on Outcomes After Pediatric Heart Transplantation

• Published in: American journal of transplantation Vol. 17; no. 6; pp. 1525 - 1539
• Main Authors: Green, D. J., Brooks, M. M., Burckart, G. J., Chinnock, R. E., Canter, C., Addonizio, L. J., Bernstein, D., Kirklin, J. K., Naftel, D. C., Girnita, D. M., Zeevi, A., Webber, S. A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 01-06-2017
• Subjects: Adolescent; Biomarkers - metabolism; Cardiomyopathy; Child; Child, Preschool; Children; clinical research/practice; disparities; ethnicity/race; Female; Follow-Up Studies; Genetic diversity; Genetic Variation; genetics; Genotype; Genotyping; Graft rejection; Graft Rejection - epidemiology; Graft Rejection - genetics; Graft Rejection - mortality; Graft Survival; health services and outcomes research; Heart; Heart diseases; Heart transplantation; Heart Transplantation - mortality; heart transplantation/cardiology; Heart transplants; Humans; Incidence; Induction therapy; Infant; Infant, Newborn; Male; patient characteristics; Pediatrics; Prognosis; Race; Racial differences; Racial Groups - genetics; Regression analysis; Risk Factors; Survival Rate; Transplantation; Transplants & implants; United States - epidemiology; United States; disparities; genetics; clinical research/practice; pediatrics; patient characteristics; ethnicity/race; heart transplantation/cardiology; health services and outcomes research
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/ajt.14153

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.
Significant racial differences persist in pediatric heart transplant outcomes and can only be partly explained by common genetic variations.