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Polymorphisms of interleukin-1α constitute independent risk factors for chronic graft-versus-host disease after allogeneic bone marrow transplantation

Lookup NU author(s): Dr Hannah Cullup, Professor Anne Dickinson, Dr Jennifer Cavet, Professor Graham Jackson, Dr Peter Middleton


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The interleukin-1 (IL-1) family of cytokines is widely involved in inflammatory processes and diseases with an inflammatory component. Polymorphisms of the IL-1α, IL-1β and IL-1Ra genes have been implicated in a number of autoimmune or inflammatory conditions, with polymorphism of the IL-1Ra gene showing association with severity of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). We compared the clinical outcomes (GVHD and survival) of 115 patients after human leucocyte antigen (HLA)-identical sibling allogeneic BMT with their genotype for two polymorphisms present in the IL-1α gene, which have been implicated in immune-related pathology. Possession of allele 2 of the IL-1α -889 polymorphism and allele 2 of the IL-1α variable number tandem repeat (VNTR) polymorphism in the donor genotype was associated with the occurrence of chronic, but not acute GVHD. A local normal population was also genotyped for these polymorphisms, and subsequent analysis identified conserved haplotypes in this gene region. Haplotypes containing allele 2 at both IL-1α -889 and IL-1α VNTR loci were extremely uncommon, suggesting that both risk alleles would be inherited independently. Both loci could therefore function as independent disease association markers. The polymorphisms of the IL-1α gene could be used to predict chronic GVHD in HLA-matched sibling transplants alongside clinical risk factors.

Publication metadata

Author(s): Cullup H, Dickinson AM, Cavet J, Jackson GH, Middleton PG

Publication type: Article

Publication status: Published

Journal: British Journal of Haematology

Year: 2003

Volume: 122

Issue: 5

Pages: 778-787

ISSN (print): 0007-1048

ISSN (electronic): 1365-2141

Publisher: Wiley-Blackwell


DOI: 10.1046/j.1365-2141.2003.04510.x

PubMed id: 12930389


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