Abstract:
BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.
journal_name
Transplantationjournal_title
Transplantationauthors
Mullighan C,Heatley S,Doherty K,Szabo F,Grigg A,Hughes T,Schwarer A,Szer J,Tait B,To B,Bardy Pdoi
10.1097/01.tp.0000111769.45088.a2subject
Has Abstractpub_date
2004-02-27 00:00:00pages
587-96issue
4eissn
0041-1337issn
1534-6080pii
00007890-200402270-00021journal_volume
77pub_type
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