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IL10 and IL10 receptor gene variation and outcomes after unrelated and related hematopoietic cell transplantation.

Tseng, Li-Hui and Storer, Barry and Petersdorf, Effie and Lin, Ming-Tseh and Chien, Jason W and Grogan, Bryan M and Malkki, Mari and Chen, Pei-Jer and Zhao, Lue P and Martin, Paul J and Hansen, John A (2009) IL10 and IL10 receptor gene variation and outcomes after unrelated and related hematopoietic cell transplantation. Transplantation, 87 (5). pp. 704-710. ISSN 1534-6080

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Abstract

BACKGROUND: Results of a previous study with human leukocyte antigen (HLA)-identical siblings showed individual and synergistic associations of single nucleotide polymorphisms in the promoter region of the recipient's IL10 gene and the donor's IL10 receptor beta (IL-10RB) gene with development of grades III-IV acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation. METHODS: In this study of 936 patients who had unrelated donors, genotypes of single nucleotide polymorphisms in the IL10 gene and the IL-10RB gene were evaluated as correlates with outcomes after transplantation. RESULTS: We found no statistically significant associations of polymorphisms at positions -3575, -2763, -1082, and -592 of the IL10 gene or codon 238 of the IL10RB gene with severe acute GVHD, extensive chronic GVHD or nonrelapse mortality after hematopoietic cell transplantation. Among HLA-matched unrelated pairs, the patient's IL10/-592 genotype and donor's IL10RB/c238 genotype showed trends suggesting individual and combined associations with grades III-IV acute GVHD similar to those observed among patients with HLA-identical sibling donors. CONCLUSIONS: Although genetic variation in IL10 pathway affects risk of acute GVHD and non-relapse mortality in HLA-identical sibling transplants, the current results indicate that genetic variation in the IL10 pathway does not significant affect these outcomes in unrelated donor transplants suggesting that the strength of the alloimmune response in the latter exceeds the anti-inflammatory activity of IL10.

Item Type: Article
Additional Information: This is a non-final version of an article published in final form in Transplantation. 2009;87(5):704-710.
DOI: 10.1097/TP.0b013e318195c474
PubMed ID: 19295315
NIHMSID: NIHMS118060
PMCID: PMC3019105
Grant Numbers: AI33484, AI49213, CA18029, CA15704, CA18221, HL088201, HL87690 , NSC94-2314-B-002-271, IBMS-CRC93-T02, NSC 95-2314-B-002-101
Keywords or MeSH Headings: Female; Genetic Variation; Genotype; Graft vs Host Disease/epidemiology/genetics; Hematopoietic Stem Cell Transplantation; Humans; Interleukin-10/genetics; Male; Polymorphism, Single Nucleotide; Receptors, Interleukin-10/genetics; Siblings; Tissue Donors/statistics & numerical data;
Subjects: Diseases > Graft vs Host
Cellular and Organismal Processes > Genetic processes
Therapeutics > Transplantation > Stem Cell transplantation
Depositing User: Library Staff
Date Deposited: 01 Jul 2009 18:11
Last Modified: 14 Feb 2012 14:42
URI: http://authors.fhcrc.org/id/eprint/308

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