IL10 and IL10 receptor gene variation and outcomes after unrelated and related hematopoietic cell transplantation.
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.
Tseng
Li-Hui
LH
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Storer
Barry
B
Petersdorf
Effie
E
Lin
Ming-Tseh
MT
Chien
Jason W
JW
Grogan
Bryan M
BM
Malkki
Mari
M
Chen
Pei-Jer
PJ
Zhao
Lue P
LP
Martin
Paul J
PJ
Hansen
John A
JA
D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D053701:Receptors, Interleukin-10 / Q000235:genetics*; D035781:Siblings; D014019:Tissue Donors / Q000706:statistics & numerical data*
D053701:Receptors, Interleukin-10; D016753:Interleukin-10