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Lookup NU author(s): Professor Anne Dickinson, Dr Peter Middleton
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Analysis of non-histocompatibility leucocyte antigen (HLA) functional genomics, together with conventional risk factors in haematopoietic stem cell transplantation (HSCT) can lead to predicting outcome in HLA-matched sibling transplant recipients. Polymorphisms of cytokine genes including tumour necrosis factor α, interleukin-10, interferon γ and interleukin (IL)-6, associate with more severe acute graft-versws-host disease (aGvHD). Donor genotype for IL-1 receptor antagonist (IL-IRa) has been associated with reduced aGvHD severity. Other genotypes (patient IL-IRa, IL-6 and donor IL-1α) have been associated with chronic GvHD, or overall survival (Vitamin D receptor and oestrogen receptor). Polymorphisms within genes associated with host defence/inflammatory responses (mannose binding lectin genes, myeloperoxidase genes and the FCγ receptors) have been associated with infections. Polymorphisms of pharmacogenes, such as methylenetetrahydrofolate-reductase, have been associated with aGvHD and other post-transplant complications. The NOD2 gene polymorphism, associated with Crohn's disease, has been shown to be associated with risk of gut GvHD. The majority of the studies have been carried out in single centre HLA-matched sibling cohorts and in relatively few matched unrelated donor transplants. This review gives an overall perspective of the current field of non-HLA genetics with regard to HSCT outcome, clinical relevance and potential application of the results to clinical management of HSCT.
Author(s): Dickinson AM, Middleton PG, Rocha V, Gluckman E, Holler E
Publication type: Review
Publication status: Published
Journal: British Journal of Haematology
Year: 2004
Volume: 127
Issue: 5
Pages: 479-490
ISSN (print): 0007-1048
ISSN (electronic): 1365-2141
URL: http://dx.doi.org/10.1111/j.1365-2141.2004.05216.x
DOI: 10.1111/j.1365-2141.2004.05216.x
PubMed id: 15566351
