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https://hdl.handle.net/2440/5859
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Type: | Journal article |
Title: | Non-HLA immunogenetic polymorphisms and the risk of complications after allogeneic hemopoietic stem-cell transplantation |
Author: | Mullighan, C. Heatley, S. Doherty, K. Szabo, F. Grigg, A. Hughes, T. Schwarer, A. Szer, J. Tait, B. To, L. Bardy, P. |
Citation: | Transplantation, 2004; 27(4):587-596 |
Publisher: | Lippincott Williams & Wilkins |
Issue Date: | 2004 |
ISSN: | 0041-1337 1534-6080 |
Statement of Responsibility: | Mullighan, Charles; Heatley, Sue; Doherty, Kathleen; Szabo, Ferenc; Grigg, Andrew; Hughes, Timothy; Schwarer, Anthony, Szer, Jeff; Tait, Brian; To, Bik; Bardy, Peter |
Abstract: | <h4>Background</h4>Existing data indicate that non-human leukocyte antigen (HLA) immunogenetic polymorphisms influence the risk of complications after allogeneic hemopoietic stem-cell transplantation. However, prior studies have been limited by small sample size and limited genotyping.<h4>Methods</h4>We examined 22 polymorphisms in 11 immunoregulatory genes including cytokines, mediators of apoptosis, and host-defense molecules by polymerase chain reaction using sequence-specific primers in 160 related myeloablative transplants. Associations were confirmed in two independent cohorts.<h4>Results</h4>An intronic polymorphism in the tumor necrosis factor gene (TNF 488A) was associated with the risk of acute graft-versus-host disease (GVHD) (odds ratio [OR] 16.9), grades II to IV acute GVHD (OR 3.3), chronic GVHD (OR 12.5), and early death posttransplant (OR 3.4). Recipient Fas -670G and donor interleukin (IL)-6 -174G were independent risk factors for acute GVHD. Recipient IL-10 ATA and Fas -670 genotype were independent risk factors for chronic GVHD. Recipient IL-1beta +3953T was associated with hepatic acute GVHD, and Fas -670G was associated with major infection.<h4>Conclusions</h4>These results highlight the potential importance of cytokine and apoptosis gene polymorphisms in stem-cell transplantation, and indicate that non-HLA genotyping may be useful to identify individuals at the highest risk of complications and new targets for therapeutic intervention. |
Keywords: | Blood Cells Humans Graft vs Host Disease Chronic Disease Genetic Predisposition to Disease Methotrexate Cyclosporine Tumor Necrosis Factor-alpha Immunosuppressive Agents Interleukins Drug Therapy, Combination Bone Marrow Transplantation Hematopoietic Stem Cell Transplantation Transplantation, Homologous Cohort Studies Polymorphism, Genetic Adult Middle Aged Female Male fas Receptor |
DOI: | 10.1097/01.TP.0000111769.45088.A2 |
Published version: | http://dx.doi.org/10.1097/01.tp.0000111769.45088.a2 |
Appears in Collections: | Aurora harvest 5 Pathology publications |
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