Relation of an Interleukin-10 Promoter Polymorphism to Graft-versus-Host Disease and Survival after Hematopoietic-Cell Transplantation
Ming-Tseh Lin, M.D., Ph.D., Barry Storer, Ph.D., Paul J. Martin, M.D., Li-Hui Tseng, M.D., Ph.D., Ted Gooley, Ph.D., Pei-Jer Chen, M.D., Ph.D., and John A. Hansen, M.D.
Background Polymorphisms in cytokine genes can influence immuneresponses, inflammation, and tissue injury and may affect theoutcome of hematopoietic stem-cell transplantation.
Methods We analyzed single-nucleotide polymorphisms in the genesfor interleukin-1, interleukin-1–receptor antagonist,interleukin-6, interleukin-10 (IL10), and tumor necrosis factor in 570 transplant recipients and their HLA-identical siblingdonors. Genotypes were tested for an association with graft-versus-hostdisease (GVHD) by multivariable analysis. A second cohort of423 transplant recipients was independently analyzed for thegenotype associations identified in the first cohort.
Results The recipient's IL10 promoter region genotype was significantlyassociated with the risk of acute GVHD in the first cohort.Analysis of all 993 transplant recipients showed that, as comparedwith the C/C genotype, the IL10 –592A/A genotype was associatedwith a decreased risk of grade III or IV acute GVHD (hazardratio, 0.4; 95 percent confidence interval, 0.2 to 0.9; P=0.02)and death in remission (hazard ratio, 0.6; 95 percent confidenceinterval, 0.3 to 1.0; P=0.05). A haplotype analysis showed thatthe IL10 –592A allele was a specific marker for a promoterhaplotype, T-C-A-T-A, defined by five polymorphisms at positions–3575, –2763, –1082, –819, and –592,respectively.
Conclusions Among recipients of hematopoietic cells from anHLA-identical sibling, the IL10 –592A allele is a markerof a favorable outcome after transplantation.
Source Information
From the Fred Hutchinson Cancer Research Center (M.-T.L., B.S., P.J.M., T.G., J.A.H.) and the University of Washington, School of Medicine (P.J.M., J.A.H.) — both in Seattle; and the Department of Medical Genetics, National Taiwan University Hospital (L.-H.T., P.-J.C.), and the College of Medicine, Graduate Institutes of Clinical Medicine (P.-J.C.), and Cancer Research Center (M.-T.L.), National Taiwan University — both in Taipei, Taiwan.
Address reprint requests to Dr. Hansen at the Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., D2-100, P.O. Box 19024, Seattle, WA 98109-1024, or at jhansen{at}fhcrc.org.
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, interleukin-1–receptor antagonist, interleukin-6, interleukin-10 (IL10), and tumor necrosis factor 
in 570 transplant recipients and their HLA-identical sibling donors. Genotypes were tested for an association with graft-versus-host disease (GVHD) by multivariable analysis. A second cohort of 423 transplant recipients was independently analyzed for the genotype associations identified in the first cohort. 
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