title: Polymorphisms of interleukin-1alpha constitute independent risk factors for chronic graft-versus-host disease after allogeneic bone marrow transplantation.
abstract: The interleukin-1 (IL-1) family of cytokines is widely involved in inflammatory processes and diseases with an inflammatory component. Polymorphisms of the IL-1alpha, IL-1beta 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-1alpha gene, which have been implicated in immune-related pathology. Possession of allele 2 of the IL-1alpha-889 polymorphism and allele 2 of the IL-1alpha 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-1alpha-889 and IL-1alpha 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-1alpha gene could be used to predict chronic GVHD in HLA-matched sibling transplants alongside clinical risk factors.
authors.affiliation: Haematological Sciences, School of Clinical Laboratory Sciences, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, UK. Hannah.Cullup@ncl.ac.uk
authors.forename: Hannah
authors.initials: H
authors.lastname: Cullup
authors.forename: Anne M
authors.initials: AM
authors.lastname: Dickinson
authors.forename: James
authors.initials: J
authors.lastname: Cavet
authors.forename: Graham H
authors.initials: GH
authors.lastname: Jackson
authors.forename: Peter G
authors.initials: PG
authors.lastname: Middleton
mesh_terms: D000328:Adult; D001855:Bone Marrow Diseases / Q000628:therapy; D016026:Bone Marrow Transplantation; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002908:Chronic Disease; D005260:Female; D005787:Gene Frequency; D006086:Graft vs Host Disease / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008232:Lymphoproliferative Disorders / Q000628:therapy; D008297:Male; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors; D014019:Tissue Donors; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
chemical_list: D007375:Interleukin-1