Influence of interleukin-10 polymorphism on the development of coronary vasculopathy following cardiac transplantation.
BACKGROUND
Interleukin-10 (IL-10), an important anti-inflammatory cytokine has been implicated in the pathogenesis of acute rejection and long term graft tolerance. Polymorphism in the IL-10 promoter at positions -1082, -819 and -592, correlates with IL-10 production. Haplotype inheritance of these alleles determines whether individuals are high, intermediate, or low producers of IL-10. We investigated the effect of this polymorphism on the development of cardiac transplant vasculopathy (CV).


METHODS
CV was defined at routine surveillance coronary angiography as any abnormality in 1 or more epicardial vessels. Recipient and donor DNA was amplified by PCR using primers to the 3 allele sites. After identifying the phenotype by electrophoresis, freedom from CV was analysed by Kaplan-Meier and the log rank test.


RESULTS
One hundred and forty eight recipients and 135 donors were studied. High, intermediate and low producers made up 26.4, 47.3 and 26.3% of recipients and 35.6, 48.2 and 16.2% of donors (P=0.42). No significant differences were noted between the phenotype groups. The recipient and donor genotypes, when considered in isolation, had no effect on the freedom from CV; recipients: P=0.85; donors: P=0.52. When the recipient and donor genotypes were combined for an individual patient the freedom from CV was again unaffected; high producing IL-10 allele in donor or recipient: P=0.76, low producing IL-10 allele in donor or recipient: P=0.51. Increasing donor age and acute rejection episodes and the presence of a high producing TGF-beta1 phenotype were independent risk factors for CV.


CONCLUSIONS
Polymorphism of the IL-10 promoter region fails to predict the development of CV and cannot be used as a genetic risk marker. This may be due to the effects of immunosuppressive treatment.
Densem
C G
CG
Cardiothoracic Transplant Unit, Wythenshawe Hospital, Manchester, UK.
Hutchinson
I V
IV
Yonan
N
N
Brooks
N H
NH
D000792:Angiography; D015415:Biomarkers; D003324:Coronary Artery Disease / Q000209:etiology*; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000009:adverse effects* / Q000473:pathology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
D015415:Biomarkers; D016753:Interleukin-10