A Monocyte chemoattractant protein-1 (MCP-1) polymorphism and outcome after renal transplantation.
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 64I 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.
Krüger
Bernd
B
Klinik für Innere Medizin II, University of Regensburg, Germany.
Schröppel
Bernd
B
Ashkan
Rami
R
Marder
Brad
B
Zülke
Carl
C
Murphy
Barbara
B
Krämer
Bernhard K
BK
Fischereder
Michael
M
D000208:Acute Disease; D000328:Adult; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics; D006085:Graft Survival; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D011110:Polymorphism, Genetic; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D018932:Chemokine CCL2