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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
Statement of
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
RMID: 0020040185
DOI: 10.1097/01.TP.0000111769.45088.A2
Appears in Collections:Pathology publications

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