Single Nucleotide Polymorphism of CC Chemokine Ligand 5 Promoter Gene in Recipients May Predict the Risk of Chronic Graft-Versus-Host Disease and its Severity After Allogeneic Transplantation

Kim, Dong Hwan; Jung, Hee Du; Lee, Nan Young; Sohn, Sang Kyun

doi:10.1097/01.tp.0000284583.15810.6e

Cited by 31 publications

(20 citation statements)

References 29 publications

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“…The Hardy-Weinberg equilibrium for the IL-17 gene polymorphism was tested using the Haploview program. 5 Multivariate Cox models were used to evaluate the hazard ratio (HR) associated with the IL-17 polymorphism. Covariates found to be significant in univariate analyses (Pp0.20) were included in the models.…”

Section: Data Management and Statistic Analysismentioning

confidence: 99%

“…2 Previous investigations have revealed that several single-nucleotide polymorphisms (SNPs), which impact on individual immune response to infections and inflammatory reactions are associated with SCT outcomes including the risk of acute GVHD. [3][4][5][6][7][8][9][10][11][12] IL-17, also known as IL-17A, is the hallmark cytokine of a new T-helper subset termed Th17. [13][14][15][16] gdT cells, macrophages and neutrophils are sources of IL-17 as well.…”

Section: Introductionmentioning

confidence: 99%

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A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT

Espinoza

Takami

Onizuka

et al. 2011

Bone Marrow Transplant

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IL-17 has an important role in the host defense against extracellular pathogens and the pathophysiology of autoimmune diseases. This study retrospectively examined the impact of a single-nucleotide polymorphism (rs2275913, G197A) in the IL-17 gene of a total 510 recipients with hematologic malignancies and their unrelated donors on the clinical outcomes in HLAmatched myeloablative (discovery study) and nonmyeloablative (validation study) BMT through the Japan Marrow Donor Program (JMDP). In the discovery study, the presence of a 197A genotype in the recipient resulted in a higher incidence of grades II-IV acute GVHD (hazard ratio (HR), 1.87; 95% confidence interval (CI), 1.23-2.85; P ¼ 0.004). The donor IL-17A genotype did not significantly influence the transplant outcomes. The validation study showed a trend toward an association of the recipient 197A genotype with an increased risk of grades III-IV acute GVHD (HR, 5.84; 95% CI,; P ¼ 0.09), as well as a significantly increased risk for chronic GVHD (HR, 3.86; 95% CI, 1.29-11.59; P ¼ 0.02). These results suggest an association of the 197A genotype in the recipient side with the development of acute GVHD.

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Section: Data Management and Statistic Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT

Espinoza

Takami

Onizuka

et al. 2011

Bone Marrow Transplant

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“…The analysis was stratified for patients with standard-risk disease and high-risk disease to take into account the already recognized prognostic differences. The variables considered were recipient age at time of transplantation, sex, recipient cytomegalovirus serosta- 32 Multivariate Cox models were used to evaluate the hazard ratio associated with the NKG2D polymorphism. Co-variates found to be statistically significant in univariate analyses (p≤0.10) were included in the models.…”

Section: Nkg2d Genotypingmentioning

confidence: 99%

NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies

et al. 2009

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BackgroundNKG2D, an activating and co-stimulatory receptor expressed on natural killer cells and T cells, plays pivotal roles in immunity to microbial infections as well as in cancer immunosurveillance. This study examined the impact of donor and recipient polymorphisms in the NKG2D gene on the clinical outcomes of patients undergoing allogeneic T-cell-replete myeloablative bone marrow transplantation using an HLA-matched unrelated donor. Design and MethodsThe NKG2D polymorphism was retrospectively analyzed in a total 145 recipients with hematologic malignancies and their unrelated donors. The patients underwent transplantation following myeloablative conditioning; the recipients and donors were matched through the Japan Marrow Donor Program. ResultsIn patients with standard-risk disease, the donor NKG2D-HNK1 haplotype, a haplotype expected to induce greater natural killer cell activity, was associated with significantly improved overall survival (adjusted hazard ratio, 0.44; 95% confidence interval, 0.23 to 0.85; p=0.01) as well as transplant related mortality (adjusted hazard ratio, 0.42; 95% confidence interval, 0.21 to 0.86; p=0.02), but had no impact on disease relapse or the development of grade II-IV acute graft-versus-host disease or chronic graft-versus-host disease. The NKG2D polymorphism did not significantly influence the transplant outcomes in patients with high-risk disease. ConclusionsThese data suggest an association between the donor HNK1 haplotype and better clinical outcome among recipients, with standard-risk disease, of bone marrow transplants from HLA-matched unrelated donors.

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“…10,11 Supporting the role of CCR5 in GVHD, a single nucleotide polymorphism (SNP) in chemokine ligand 5 (CCL5, also known as RANTES) has been significantly associated with a greater incidence of chronic graft-versus-host disease (cGVHD). 12 The authors of another study 13 demonstrated that recipients with the nonfunctional CCR5⌬32 allele were less likely to develop acute graft-versushost disease (aGVHD), and other authors [14][15][16] have found CCR5 promoter polymorphisms to be predictive of the response to chemotherapy in leukemia and in the likelihood of cytomegalovirus and Epstein-Barr virus reactivation after HSCT.…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11][12][13][14][15][16] In particular, blockade or lack of the chemokine receptors CCR2 and CCR5 on donor leukocytes by administration of anti-CCR5 antibody or infusion of CCR2 Ϫ/Ϫ T cells reduces the incidence of GVHD in animal models. 10,11 Supporting the role of CCR5 in GVHD, a single nucleotide polymorphism (SNP) in chemokine ligand 5 (CCL5, also known as RANTES) has been significantly associated with a greater incidence of chronic graft-versus-host disease (cGVHD).…”

Section: Introductionmentioning

confidence: 99%

Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation

McDermott

Conway

Wang

et al. 2010

Blood

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Despite continual improvement, morbidity and mortality after hematopoietic stem cell transplantation (HSCT) remain high. The importance of chemokines in HSCT lies in their regulation of immune responses that determine transplantation outcomes. We investigated the role of recipient and donor chemokine system gene polymorphisms by using a candidate gene approach on the incidence of graft-versus-host disease and posttransplantation outcomes in 1370 extensively human leukocyte antigen-matched, unrelated donor-recipient pairs by using multivariate Cox regression models. Our analysis identified that recipients homozygous for a common CCR5 haplotype (H1/H1) had better disease-free survival (DFS; P ‫؍‬ .005) and overall survival (P ‫؍‬ .021). When the same genotype of both the donor and recipient were considered in the models, a highly significant association with DFS and overall survival was noted (P < .001 and P ‫؍‬ .007, respectively) with absolute differences in survival of up to 20% seen between the groups at 3 years after transplantation (50% DFS for pairs with recipient CCR5 H1/H1 vs 30% for pairs with donor CCR5 H1/H1). This finding suggests that donor and/or recipient CCR5 genotypes may be associated with HSCT outcome and suggests new diagnostic and therapeutic strategies for optimizing therapy. (Blood.

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Single Nucleotide Polymorphism of CC Chemokine Ligand 5 Promoter Gene in Recipients May Predict the Risk of Chronic Graft-Versus-Host Disease and its Severity After Allogeneic Transplantation

Abstract: The CCL5 promoter gene polymorphism of recipients was associated with the risk of cGVHD and its severity. The current study suggested an involvement of CCL5 in leukocyte trafficking for the development of cGVHD.

Cited by 31 publications

References 29 publications

A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT

A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT

NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies

Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation

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