Relation of an interleukin-23 receptor gene polymorphism to graft-versus-host disease after hematopoietic-cell transplantation

被引:53
作者
Elmaagacli, A. H. [1 ]
Koldehoff, M. [1 ]
Landt, O. [2 ]
Beelen, D. W. [1 ]
机构
[1] Univ Hosp Essen, Dept Bone Marrow Transplant, D-45122 Essen, Germany
[2] TIB MOLBIOL Syntheselabor GmbH, Berlin, Germany
关键词
IL-23R; SNP; acute GVHD; transplant;
D O I
10.1038/sj.bmt.1705980
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Polymorphisms in cytokine genes can influence immune responses and inflammation and thereby affecting the outcome of hematopoietic stem-cell transplantation. We analyzed a single-nucleotide polymorphism in the gene for the interleukin-23 receptor (IL-23R) (1142G > A) in a cohort of 221 transplant recipients and their human leukocyte antigen (HLA)-identical sibling donors and in a second cohort of 186 transplant recipients and their HLA-identical unrelated donors. Genotypes were tested for an association with graft-versus-host disease (GVHD) by multivariate analysis. The donor's IL-23R genotype was significantly associated with a reduced risk of acute GVHD in both cohorts for patients after transplant. Analysis of all 407 transplant recipients showed that IL-23R (1142G > A, Arg381Gln) genotype of the donor was associated with a decreased risk of grades 2-4 acute GVHD (31.6 compared to 51.0%, P=0.02) and grades 3-4 severe acute GVHD (3.9 compared to 23.4%, P=0.003). Death in remission was significantly lower in patients transplanted from donors with variant IL23-R (11.7 versus 27.7%, P=0.028), whereas overall survival or relapse rates were not influenced significantly by the IL-23R genotype. Among recipients of hematopoietic cells from HLA-identical donors, the IL-23R (Arg381Gln) gene variant on the donor side has a protective effect on the occurrence of acute GVHD in recipients after transplantation.
引用
收藏
页码:821 / 826
页数:6
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