title: Interleukin-1 genotype and outcome of unrelated donor bone marrow transplantation.
abstract: The interleukin 1 (IL-1) gene family includes three members (IL-1-alpha, IL-1-beta and IL-1Ra) that mediate immune and inflammatory responses through two specific cell surface receptors. Cytosine to thymine transitions at codons -889 and -511 in the IL-1-alpha and IL-1-beta genes, respectively, and an 86-base pair repeat in the IL-1Ra are believed to influence gene transcription. We have genotyped these three polymorphisms in 90 donor/recipient pairs undergoing unrelated donor bone marrow transplantation (BMT) at the University of Minnesota. We found no association between the occurrence of acute GVHD and donor and/or recipient polymorphisms of any of the three IL-1 genes. The presence of at least one IL-1alpha- 889 T allele in the donor was associated with significantly improved survival in univariate analysis (survival at 1 year 40% C/C donor, 68% T/C donor, 75% T/T donor, P < 0.01). Multiple regression analysis showed that if the donor and recipient each possessed the IL-1alpha T allele there was significantly improved survival [relative risk (RR) 0.2, P < 0.01] and decreased treatment-related mortality (TRM; RR 0.2, P = 0.01). The presence of the IL-1beta T allele in donor and recipient was also associated with improved survival (RR 0.2, P < 0.01) and decreased TRM (RR 0.1, P < 0.01). These data suggest that donor polymorphism in IL-1alpha and IL-1beta might influence survival after unrelated donor BMT, but does not alter risk of GVHD.
authors.affiliation: Pediatrics Department, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA. macmi002@umn.edu
authors.forename: Margaret L
authors.initials: ML
authors.lastname: MacMillan
authors.forename: Gretchen A
authors.initials: GA
authors.lastname: Radloff
authors.forename: Todd E
authors.initials: TE
authors.lastname: DeFor
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics; D006402:Hematologic Diseases / Q000628:therapy; D006801:Humans; D007223:Infant; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012044:Regression Analysis; D016019:Survival Analysis; D014184:Transplantation, Homologous
chemical_list: D007375:Interleukin-1