BACKGROUND: Both chemokines and adhesion molecules mediate allograft rejection by recruiting leukocytes into the allograft. We investigated the association of six single nucleotide polymorphisms (SNPs) located in interleukin (IL)-8, CXCR1, CXCR2, and selectin with kidney allograft outcomes. METHODS: The promoter regions of CXCR1 and CXCR2 were sequenced directly to find SNPs. Reporter gene assay was performed to determine the transcriptional activity of CXCR2 promoter polymorphisms. The association of SNPs in IL-8, CXCR1, CXCR2, and selectin with both acute rejection and estimated glomerular filtration rate at 1-year posttransplant was analyzed in 216 donor-recipient pairs of kidney transplantation. RESULTS: The donor GA/AA genotypes of CXCR1 -2668G/A (rs2671222) were associated with increased risk for acute rejection even after adjusting for covariates such as gender, diabetes, preemptive transplantation, immunosuppressive regimen, relationship with the donor, and human leukocyte antigen mismatch (adjusted odds ratio 3.56; 95% confidence interval 1.37-9.27; P=0.009). Although the transcriptional activity of the CXCR2 variant promoter was 2.6-fold higher than that of the wild-type promoter (P=0.039), no significant association was observed between CXCR2 polymorphisms and kidney allograft outcomes. SNPs of IL-8, L-selectin, and E-selectin were not associated with kidney allograft outcomes. CONCLUSION: The donor CXCR1 -2668 GA/AA genotypes were an independent risk factor for acute rejection in kidney transplantation.
BACKGROUND: Both chemokines and adhesion molecules mediate allograft rejection by recruiting leukocytes into the allograft. We investigated the association of six single nucleotide polymorphisms (SNPs) located in interleukin (IL)-8, CXCR1, CXCR2, and selectin with kidney allograft outcomes. METHODS: The promoter regions of CXCR1 and CXCR2 were sequenced directly to find SNPs. Reporter gene assay was performed to determine the transcriptional activity of CXCR2 promoter polymorphisms. The association of SNPs in IL-8, CXCR1, CXCR2, and selectin with both acute rejection and estimated glomerular filtration rate at 1-year posttransplant was analyzed in 216 donor-recipient pairs of kidney transplantation. RESULTS: The donor GA/AA genotypes of CXCR1-2668G/A (rs2671222) were associated with increased risk for acute rejection even after adjusting for covariates such as gender, diabetes, preemptive transplantation, immunosuppressive regimen, relationship with the donor, and human leukocyte antigen mismatch (adjusted odds ratio 3.56; 95% confidence interval 1.37-9.27; P=0.009). Although the transcriptional activity of the CXCR2 variant promoter was 2.6-fold higher than that of the wild-type promoter (P=0.039), no significant association was observed between CXCR2 polymorphisms and kidney allograft outcomes. SNPs of IL-8, L-selectin, and E-selectin were not associated with kidney allograft outcomes. CONCLUSION: The donorCXCR1 -2668 GA/AA genotypes were an independent risk factor for acute rejection in kidney transplantation.
Authors: Gero Hütter; Martin Neumann; Daniel Nowak; Stefan Klein; Harald Klüter; Wolf-K Hofmann Journal: J Inflamm (Lond) Date: 2011-10-26 Impact factor: 4.981