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Right arrow Transplantation - heart

Ann Thorac Surg 2004;77:875-880
© 2004 The Society of Thoracic Surgeons


Original article: cardiovascular

Influence of IFN-{gamma} polymorphism on the development of coronary vasculopathy after cardiac transplantation

Cameron G. Densem, MRCPa*, Ian V. Hutchinson, BSc, PhDb, Nizar Yonan, FRCSb, Nicholas H. Brooks, FRCPa

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)-{gamma} 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-{gamma} is expressed early after transplantation and neutralization or genetic absence of the cytokine can abrogate CV development. The expression of IFN-{gamma} is influenced by a dinucleotide repeat in the first intron of the IFN-{gamma} gene. We investigated the effect of this polymorphism on the development of CV.

METHODS: Using sequence specific primers to the IFN-{gamma} 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-{gamma} producing genotype and the development of CV diagnosed by routine surveillance posttransplant angiography.

RESULTS: High, intermediate, and low IFN-{gamma} producers made up 29.2%, 44.4%, 26.4% and 24.6%, 40.3%, 35.1% of recipients and donors respectively (p = NS). IFN-{gamma} 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-{gamma} gene does not influence CV development and cannot be used as a genetic risk marker.







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