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Donor single nucleotide polymorphism in the CCR9 gene affects the incidence of skin GVHD
- Source :
- ResearcherID
- Publication Year :
- 2009
- Publisher :
- Springer Science and Business Media LLC, 2009.
-
Abstract
- The interactions between chemokines and their receptors may have an important role in initiating GVHD after allogeneic hematopoietic SCT (allo-HSCT). CCL25 and CCR9 are unique because they are exclusively expressed in epithelial cells and in Peyer's patches of the small intestine. We focused on rs12721497 (G926A), one of the non-synonymous single nucleotide polymorphisms (SNPs) in the CCR9 gene, and analyzed the SNP of donors in 167 consecutive patients who received allo-HSCT from an HLA-identical sibling donor. Genotypes were tested for associations with acute and chronic GVHD in each organ and transplant outcome. Multivariate analyses showed that the genotype 926AG was significantly associated with the incidence of acute stageor =2 skin GVHD (hazard ratio: 3.2; 95% confidence interval (95% CI): 1.1-9.1; P=0.032) and chronic skin GVHD (hazard ratio: 4.1; 95% CI: 1.1-15; P=0.036), but not with GVHD in other organs or with relapse, non-relapse mortality or OS. To clarify the functional differences between genotypes, each SNP in retroviral vectors was transfected into Jurkat cells. In chemotaxis assays, the 926G transfectant showed greater response to CCL25 than the 926A transfectant. In conclusion, more active homing of CCR9-926AG T cells to Peyer's patches may produce changes in Ag presentation and result in increased incidence of skin GVHD.
- Subjects :
- Adult
Male
medicine.medical_specialty
Chemokine
Adolescent
Graft vs Host Disease
Single-nucleotide polymorphism
Polymorphism, Single Nucleotide
Skin Diseases
Jurkat cells
Jurkat Cells
Receptors, CCR
immune system diseases
Internal medicine
Immunopathology
medicine
Humans
Transplantation
Hematology
biology
business.industry
Incidence
Hazard ratio
Hematopoietic Stem Cell Transplantation
Middle Aged
medicine.disease
Tissue Donors
Chemotaxis, Leukocyte
Treatment Outcome
surgical procedures, operative
Graft-versus-host disease
Immunology
biology.protein
Female
Gene polymorphism
business
Subjects
Details
- ISSN :
- 14765365 and 02683369
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- Bone Marrow Transplantation
- Accession number :
- edsair.doi.dedup.....30a69c6cf2eb733e53f6d5c4055e36b5