TY - JOUR
T1 - Relation of an Interleukin-10 Promoter Polymorphism to Graft-versus-Host Disease and Survival after Hematopoietic-Cell Transplantation
AU - Lin, Ming Tseh
AU - Storer, Barry
AU - Martin, Paul J.
AU - Tseng, Li Hui
AU - Gooley, Ted
AU - Chen, Pei Jer
AU - Hansen, John A.
PY - 2003/12/4
Y1 - 2003/12/4
N2 - BACKGROUND: Polymorphisms in cytokine genes can influence immune responses, inflammation, and tissue injury and may affect the outcome of hematopoietic stem-cell transplantation. METHODS: We analyzed single-nucleotide polymorphisms in the genes for interleukin-1β, interleukin-1-receptor antagonist, interleukin-6, interleukin-10 (IL10), and tumor necrosis factor a 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. RESULTS: 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. CONCLUSIONS: Among recipients of hematopoietic cells from an HLA-identical sibling, the IL10-592A allele is a marker of a favorable outcome after transplantation.
AB - BACKGROUND: Polymorphisms in cytokine genes can influence immune responses, inflammation, and tissue injury and may affect the outcome of hematopoietic stem-cell transplantation. METHODS: We analyzed single-nucleotide polymorphisms in the genes for interleukin-1β, interleukin-1-receptor antagonist, interleukin-6, interleukin-10 (IL10), and tumor necrosis factor a 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. RESULTS: 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. CONCLUSIONS: Among recipients of hematopoietic cells from an HLA-identical sibling, the IL10-592A allele is a marker of a favorable outcome after transplantation.
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U2 - 10.1056/NEJMoa022060
DO - 10.1056/NEJMoa022060
M3 - Article
C2 - 14657427
AN - SCOPUS:84983719872
SN - 0028-4793
VL - 349
SP - 2201
EP - 2210
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 23
ER -