PMID- 12239249 OWN - NLM STAT- MEDLINE DCOM- 20030307 LR - 20190607 IS - 1046-6673 (Print) IS - 1046-6673 (Linking) VI - 13 IP - 10 DP - 2002 Oct TI - A Monocyte chemoattractant protein-1 (MCP-1) polymorphism and outcome after renal transplantation. PG - 2585-9 AB - 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. FAU - Kruger, Bernd AU - Kruger B AD - Klinik fur Innere Medizin II, University of Regensburg, Germany. FAU - Schroppel, Bernd AU - Schroppel B FAU - Ashkan, Rami AU - Ashkan R FAU - Marder, Brad AU - Marder B FAU - Zulke, Carl AU - Zulke C FAU - Murphy, Barbara AU - Murphy B FAU - Kramer, Bernhard K AU - Kramer BK FAU - Fischereder, Michael AU - Fischereder M LA - eng GR - R01 AI 49289-01/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Am Soc Nephrol JT - Journal of the American Society of Nephrology : JASN JID - 9013836 RN - 0 (Chemokine CCL2) SB - IM MH - Acute Disease MH - Adult MH - Chemokine CCL2/biosynthesis/*genetics MH - Female MH - Genotype MH - Graft Rejection/genetics MH - Graft Survival MH - Humans MH - *Kidney Transplantation MH - Male MH - Middle Aged MH - Monocytes/metabolism MH - *Polymorphism, Genetic MH - Transplantation, Homologous MH - Treatment Outcome EDAT- 2002/09/20 10:00 MHDA- 2003/03/08 04:00 CRDT- 2002/09/20 10:00 PHST- 2002/09/20 10:00 [pubmed] PHST- 2003/03/08 04:00 [medline] PHST- 2002/09/20 10:00 [entrez] AID - 10.1097/01.asn.0000031701.53792.54 [doi] PST - ppublish SO - J Am Soc Nephrol. 2002 Oct;13(10):2585-9. doi: 10.1097/01.asn.0000031701.53792.54.