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

Br J Haematol. 2003 Sep;122(5):778-87. doi: 10.1046/j.1365-2141.2003.04510.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bone Marrow Diseases / therapy
  • Bone Marrow Transplantation*
  • Case-Control Studies
  • Chi-Square Distribution
  • Chronic Disease
  • Female
  • Gene Frequency
  • Graft vs Host Disease / immunology*
  • Haplotypes
  • Humans
  • Interleukin-1 / genetics*
  • Lymphoproliferative Disorders / therapy
  • Male
  • Polymorphism, Genetic*
  • Regression Analysis
  • Risk Factors
  • Tissue Donors
  • Transplantation Immunology
  • Transplantation, Homologous


  • Interleukin-1