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Ann Thorac Surg 2004;77:875-880
© 2004 The Society of Thoracic Surgeons
polymorphism on the development of coronary vasculopathy after cardiac transplantation
a Cardiothoracic Transplant Unit, Wythenshawe Hospital, United Kingdom
b and School of Biological Sciences, Manchester University, Manchester, United Kingdom
Accepted for publication July 30, 2003.
* Address reprint requests to Dr Densem, Department of Cardiology, Wythenshawe Hospital, Southmoor Rd, Wythenshawe, Manchester M23 9LT, UK
e-mail: cameron.d{at}virgin.net
BACKGROUND: The development of coronary vasculopathy (CV) limits survival after cardiac transplantation. Interferon (IFN)-
is an important immunomodulator affecting the growth and function of T cells and macrophages, free radical formation, adhesion molecule, and MHC class I and II expression, which are important processes for CV formation. IFN-
is expressed early after transplantation and neutralization or genetic absence of the cytokine can abrogate CV development. The expression of IFN-
is influenced by a dinucleotide repeat in the first intron of the IFN-
gene. We investigated the effect of this polymorphism on the development of CV.
METHODS: Using sequence specific primers to the IFN-
polymorphic region, polymerase chain reaction (PCR) and gel electrophoresis identified the genotype in 144 cardiac transplant recipients and 134 donors. An association was sought between the presence of a high, intermediate or low IFN-
producing genotype and the development of CV diagnosed by routine surveillance posttransplant angiography.
RESULTS: High, intermediate, and low IFN-
producers made up 29.2%, 44.4%, 26.4% and 24.6%, 40.3%, 35.1% of recipients and donors respectively (p = NS). IFN-
polymorphism in cardiac graft recipients had no impact on the time to first diagnosis of CV; high producers 4.03 years (± 129.9 days), intermediate producers 3.40 years (± 79.7 days), low producers 4.01 years (± 102.9 days); p = 0.16. Similar results were found on investigating donor polymorphism; high producers (3.68 years ± 120.1 days), intermediate producers (3.83 years ± 105.9 days), low producers (3.3 years ± 77.7 days); p = 0.35. Multivariate analysis identified the number of rejection episodes of ISHLT grade 3 or greater and increasing donor age to be independent risk factors for CV development.
CONCLUSIONS: Dinucleotide repeat polymorphism in the first intron of the human IFN-
gene does not influence CV development and cannot be used as a genetic risk marker.
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