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Polymorphisms of interleukin‐1α constitute independent risk factors for chronic graft‐versus‐host disease after allogeneic bone marrow transplantation
Author(s) -
Cullup Hannah,
Dickinson Anne M.,
Cavet James,
Jackson Graham H.,
Middleton Peter G.
Publication year - 2003
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04510.x
Subject(s) - immunology , haplotype , allele , genotype , human leukocyte antigen , biology , graft versus host disease , transplantation , variable number tandem repeat , disease , genetics , medicine , gene , antigen , stem cell
Summary. 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.