Cardiology in the Young



Original Article

Polymorphisms in cytokine genes do not predict progression to end-stage heart failure in children


Steven A. Webber a1c1, Gerard J. Boyle a1, Steven Gribar a1, Yuk Law a1, Pamela Bowman a1, Susan A. Miller a1, Mohammed R. Awad a2, Mamun Ahmed a2, Joan Martell a2 and Adriana Zeevi a2
a1 Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh and Thomas E. Starzl Transplant Institute, Pittsburgh, USA
a2 Department of Pathology, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh and Thomas E. Starzl Transplant Institute, Pittsburgh, USA

Article author query
webber sa   [PubMed][Google Scholar] 
boyle gj   [PubMed][Google Scholar] 
gribar s   [PubMed][Google Scholar] 
law y   [PubMed][Google Scholar] 
bowman p   [PubMed][Google Scholar] 
miller sa   [PubMed][Google Scholar] 
awad mr   [PubMed][Google Scholar] 
ahmed m   [PubMed][Google Scholar] 
martell j   [PubMed][Google Scholar] 
zeevi a   [PubMed][Google Scholar] 

Abstract

A number of cytokines have been implicated in the pathophysiology of congestive heart failure. Genetic polymorphisms of several cytokine genes are known to result in altered gene expression, enabling us to characterize patients as "high" or "low" producers of specific cytokines. We speculate that the cytokine genotypes for a population of children who underwent heart transplantation for end-stage ventricular failure due to cardiomyopathy or congenital heart disease would be enriched for "high producers" of pro-inflammatory cytokines and "low producers" of anti-inflammatory cytokines. Methods: Cytokine genotyping was performed for the following cytokines on 94 transplanted children using polymerase chain reaction-sequence specific technique: tumor necrosis factor-α (−308), interleukin 10 (−1082, −819, −592), interleukin 6 (−174), transforming growth factor-β1(codons 10 & 25), and interferon-γ (+874). Patients with ventricular failure after transplantation for dilated cardiomyopathy, numbering 37, or for congenital heart disease, numbering 34, were compared to 15 children transplanted for structural disease, such as hypoplastic left heart syndrome, without ventricular failure, and to data from healthy children. An additional 8 children with restrictive or hypertrophic cardiomyopathy were also studied. Results: No differences in genotypic distribution were seen between the groups, and all patients were comparable to genotypic distributions as assessed from published normal data. Conclusion: No evidence is found to support the hypothesis that these polymorphisms for cytokine genes influence progression to end-stage heart failure in children undergoing transplantation because of cardiomyopathy or congenital heart disease.

(Published Online August 15 2006)
(Accepted May 15 2002)


Key Words: Heart failure; cytokines; genetic polymorphisms.

Correspondence:
c1 Correspondence to: Steven Webber, MBChB, Division of Cardiology, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA. Tel: 412 692 5541; Fax: 412 692 6991; E-mail: steve.webber@chp.edu