Relation of an Interleukin-10 Promoter Polymorphism to Graft-versus-Host Disease and Survival after Hematopoietic-Cell Transplantation

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Abstract
Polymorphisms in cytokine genes can influence immune responses, inflammation, and tissue injury and may affect the outcome of hematopoietic stem-cell transplantation. We analyzed single-nucleotide polymorphisms in the genes for interleukin-1β, interleukin-1–receptor antagonist, interleukin-6, interleukin-10 (IL10), and tumor necrosis factor α 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. The recipient's IL10 promoter region genotype was significantly associated with the risk of acute GVHD in the first cohort. Analysis of all 993 transplant recipients showed that, as compared with the C/C genotype, the IL10 –592A/A genotype was associated with a decreased risk of grade III or IV acute GVHD (hazard ratio, 0.4; 95 percent confidence interval, 0.2 to 0.9; P=0.02) and death in remission (hazard ratio, 0.6; 95 percent confidence interval, 0.3 to 1.0; P=0.05). A haplotype analysis showed that the IL10 –592A allele was a specific marker for a promoter haplotype, T-C-A-T-A, defined by five polymorphisms at positions –3575, –2763, –1082, –819, and –592, respectively. Among recipients of hematopoietic cells from an HLA-identical sibling, the IL10 –592A allele is a marker of a favorable outcome after transplantation.