Zusammenfassung
Among the factors modulating transplant rejection and cardiovascular disease, chemokines and their respective receptors deserve special attention. In this respect, increased expression of MCP-1 and the corresponding receptor CCR2 have been demonstrated in renal transplant rejection and coronary artery disease. The impact of the MCP-1-2518G and CCR2-64I genotypes on renal allograft function was ...
Zusammenfassung
Among the factors modulating transplant rejection and cardiovascular disease, chemokines and their respective receptors deserve special attention. In this respect, increased expression of MCP-1 and the corresponding receptor CCR2 have been demonstrated in renal transplant rejection and coronary artery disease. The impact of the MCP-1-2518G and CCR2-64I genotypes on renal allograft function was investigated in 232 patients who underwent transplantation over an 11-yr period. Genomic DNA was genotyped using PCR with sequence-specific primers followed by restriction fragment length polymorphism analysis. Eighteen (7.8%) patients were homozygous for the MCP-1-2518G mutation. The G/G allele of MCP-1 -2518 behaved as a determinant for long-term allograft survival and resulted in reduction of the mean graft survival, as compared with the heterozygous (A/G) or wild-type (A/A) allele (67 +/- 14 versus 95 +/- 4 mo; Log rank P = 0.0052). The 641 mutation of CCR2 had no effect on kidney graft failure (93 +/- 6 and 91 +/- 5 mo, respectively; P = 0.81). None of the investigated polymorphisms showed a significant shift in gene frequency in acute rejection and rejection-free groups. In conjunction with these findings, peripheral blood mononuclear cells from kidney transplant recipients carrying the G-allele were characterized by a 2.5-fold higher MCP-1 secretion (P < 0.05). In conclusion, recipients of renal transplants homozygous for the -2518 G mutation of the MCP-1 gene are at risk for premature kidney graft failure. This variant of MCP-1 may be a future predictor for long-term kidney graft failure.
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