Format

Send to

Choose Destination
J Am Coll Cardiol. 2009 May 19;53(20):1909-17. doi: 10.1016/j.jacc.2009.02.027.

Recipient genotype is a predictor of allograft cytokine expression and outcomes after pediatric cardiac transplantation.

Author information

1
Department of Pediatric Cardiology, Columbia University, Morgan Stanley Children's Hospital of New York-Presbyterian, New York, New York, USA.

Abstract

OBJECTIVES:

This study sought to investigate the influence of recipient renin-angiotensin-aldosterone system (RAAS) genotype on cardiac function, rejection, and outcomes after heart transplantation.

BACKGROUND:

The RAAS influences cardiac function and up-regulates inflammatory/immune pathways. Little is known about the effect of recipient RAAS polymorphisms in pediatric cardiac transplantation.

METHODS:

Patients <25 years of age, after cardiac transplantation, were enrolled (2003 to 2008) and genotyped for polymorphisms in genes associated with RAAS upregulation: AGT-G, ACE-D, AGTR1-C, CYP11B2-G, and CMA-A. Presence of at least 1 high-risk allele was defined as a high-risk genotype. Univariable and multivariable associations between genotypes and outcomes were assessed in time-dependent models using survival, logistic, or linear regression models. Biopsy samples were immunostained for interleukin (IL)-6, transforming growth factor (TGF)-beta, and tumor necrosis factor (TNF)-alpha during rejection and quiescence.

RESULTS:

A total of 145 patients were studied, 103 primary cohort and 42 replication cohort; 81% had rejection, 51% had graft dysfunction, and 13% had vasculopathy, 7% died and 8% underwent re-transplantation. A higher number of homozygous high-risk RAAS genotypes was associated with a higher risk of graft dysfunction (hazard ratio [HR]: 1.5, p = 0.02) and a higher probability of death (HR: 2.5, p = 0.04). The number of heterozygous high-risk RAAS genotypes was associated with frequency of rejection (+0.096 events/year, p < 0.001) and rejection-associated graft dysfunction (+0.37 events/year, p = 0.002). IL-6 and TGF-beta were markedly upregulated during rejection in patients with >/=2 high-risk RAAS genotypes.

CONCLUSIONS:

Recipient RAAS polymorphisms are associated with a higher risk of rejection, graft cytokine expression, graft dysfunction, and a higher mortality after cardiac transplantation. This may have implications for use of RAAS inhibitors in high-risk patients after transplantation.

PMID:
19442892
DOI:
10.1016/j.jacc.2009.02.027
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center