Abstract
Among the factors modulating transplant rejection, chemokines and their respective receptors deserve special attention. Increased expression of monocyte chemoattractant protein-1 (MCP-1) and its corresponding receptor (chemokine receptor-2, CCR2) has been implicated in renal transplant rejection. To determine the impact of the MCP-1-2518G and CCR2-64I genotypes on renal allograft function, 167 Korean patients who underwent transplantation over a 25-year period were evaluated. Genomic DNA was genotyped using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Fifty-five (32.9%) patients were homozygous for the MCP-1-2518G polymorphism. Nine (5.4%) patients were homozygous for the CCR2-64I polymorphism. None of the investigated polymorphism showed a significant shift in long-term allograft survival. However, a significant increase was noted for the risk of late acute rejection in recipients who were homozygous for the MCP-1-2518G polymorphism (OR, 2.600; 95% CI, 1.125–6.012; P = 0.022). There was also an association between the MCP-1-2518G/G genotype and the number of late acute rejection episodes (P = 0.024). Although there was no difference in the incidence of rejection among recipients stratified by the CCR2-V64I genotype, recipients with the CCR2-V64I GG genotype in combination with the MCP-1-2518G/G genotype had a significantly higher risk of acute or late acute rejection among the receptor-ligand combinations (P = 0.006, P = 0.008, respectively). The MCP-1 variant may be a marker for risk of late acute rejection in Korean patients.
Highlights
Despite advances in immunosuppression and the overall medical care of renal transplant recipients, which have led to an improvement in allograft survival, chronic renal allograft rejection continues to be a major impediment to successful organ transplantation (Milford, 1994)
Individuals with or without the monocyte chemoattractant protein-1 (MCP-1)-2518G/G genotype did not differ with respect to other risk factors for rejection frequency and allograft failure such as donor age, ethnic background, living donor, HLA-mismatch, immunosuppressive therapy, recipient age and gender and the serum creatinine level of the donor
Individuals with the MCP-1-2518G/G genotype had a higher occurrence of late acute rejection than individuals with other genotypes (Table 1)
Summary
Despite advances in immunosuppression and the overall medical care of renal transplant recipients, which have led to an improvement in allograft survival, chronic renal allograft rejection continues to be a major impediment to successful organ transplantation (Milford, 1994). Other than those at the HLA locus, are attractive factors that might explain some of the clinical heterogeneity with regard to outcome of organ transplantation. Genetic variation may influence the function or expression of key immunoregulatory molecules that mediate transplant rejection. Monocytes and Teffector cells are directed into the transplant and produce a characteristic tubular or vascular infiltrate (Lalor & Adams, 2001). The expression of the CC-chemokine MCP-1 together with the corresponding chemokine receptor CCR2 can be detected in mononuclear cells infiltrating the kidney graft (Nadeau et al, 1995; Pavlakis et al, 1996; Grandaliano et al, 1997; Nagano et al, 1997; Robertson et al, 2000; Segerer et al, 2001)
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