Polymorphisms in cytokine genes do not predict progression to end-stage heart failure in children.
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-alpha (-308), interleukin 10 (-1082, -819, -592), interleukin 6 (-174), transforming growth factor-beta1 (codons 10 & 25), and interferon-gamma (+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.


CONCLUSIONS
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.
Webber
Steven A
SA
Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, PA 15213, USA. steve.webber@chp.edu
Boyle
Gerard J
GJ
Gribar
Steven
S
Law
Yuk
Y
Bowman
Pamela
P
Miller
Susan A
SA
Awad
Mohammed R
MR
Ahmed
Mamun
M
Martell
Joan
J
Zeevi
Adriana
A
D002648:Child; D016207:Cytokines / Q000235:genetics*; D018450:Disease Progression; D005838:Genotype; D006331:Heart Diseases / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D011110:Polymorphism, Genetic; D011379:Prognosis; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma