Genetic polymorphisms impact the risk of acute rejection in pediatric heart transplantation: A multi-institutional study

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

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52 Scopus citations

Abstract

OBJECTIVE.: The objective of this study was to determine the association between the genetic polymorphisms of proinflammatory and regulatory cytokines and long-term rates of repeat and late acute rejection episodes in pediatric heart transplant (PHTx) recipients. METHODS.: Three hundred twenty-three PHTx recipients: 205 White non-Hispanic, 43 Black non-Hispanic, and 75 Hispanic were analyzed for time to first repeat and late acute rejection episodes by race, age at transplantation, and gene polymorphism (interleukin [IL]-6, -174 G/C, IL-10, -1082 G/A, -819 C/T, 592 C/A; vascular endothelial growth factor (VEGF) -2578 C/A, -460 C/T, +405 C/G; tumor necrosis factor alpha (TNF-α)-308 G/A). RESULTS.: Recipient black race and older age at transplant were risk factors for both repeat and late rejections, though black race was more significantly related to late rejection (P=0.006). Individually, TNF-α high, IL-6 high, VEGF high, and IL-10 low phenotypes did not impact the risk of repeat or late rejection. However, the combination VEGF high/IL-6 high and IL-10 low was associated with increased estimated risk of late rejection (P=0.0004) and only marginally with repeat rejection (P=0.051). In a multivariate analysis, adjusting for age and race, VEGF high/IL-6 high and IL-10 low still remained an independent risk factor for late acute rejection (RR=1.91, P<0.001). CONCLUSION.: This is the largest multicenter study to document the impact of genetic polymorphism combinations on PHTx recipients' outcome. The high proinflammatory (VEGF high/IL-6 high) and lower regulatory (IL-10 low) cytokine gene polymorphism profile exhibited increased risk for late rejection, irrespective of age and race/ethnicity.

Original languageEnglish
Pages (from-to)1632-1639
Number of pages8
JournalTransplantation
Volume85
Issue number11
DOIs
StatePublished - Jun 15 2008

Keywords

  • Gene polymorphism
  • Heart
  • Multi-institutional study
  • Pediatric
  • Race/ethnicity
  • Transplantation

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