Biomedical subjects

Brad Marder

Publications and source records attributed to Brad Marder.

3 recordsLinked to original sources

PubMed2003

Genetic variability and transplantation.

PURPOSE OF REVIEW: The purpose of this review is to summarize recent advances within the area of genetic polymorphisms with a specific emphasis on renal transplantation, and to discuss the potential clinical applications. RECENT FINDINGS: Due to recent advances in molecular techniques, there has been an abundance of publications describing genetic variability in molecules relevant to transplant outcome. Many studies are now demonstrating associations between polymorphisms in these candidate genes and outcomes in organ transplantation. SUMMARY: These studies emphasize the potential role of genetic variability in transplantation, and provide the rationale for large prospective studies to clearly define the potential benefits of genotyping in the risk stratification of transplant recipients.

Animals↗

PubMed2002

Analysis of gene polymorphisms in the regulatory region of MCP-1, RANTES, and CCR5 in liver transplant recipients.

Chemokines and their receptors play a major role in the inflammatory and immune responses that mediate allograft outcome. The production of some chemokines varies among individuals and these variations may be determined by genetic polymorphisms, most commonly within the regulatory region of the gene. We investigated whether the functional polymorphisms of the chemokines RANTES, MCP-1 and chemokine receptor CCR5 are associated with the incidence of acute rejection and long-term liver graft survival. Two hundred nine liver transplant recipients were genotyped using polymerase chain reaction sequence-specific primers for the following polymorphisms: RANTES-28, MCP-1 -2518, and CCR5-59029. There was no association with any of the three genotypes and the incidence of acute rejection episodes. In addition, no association of RANTES-28, MCP-1 -2518, or CCR5 -59029 variants with long-term liver graft survival was found. In conclusion, variants of RANTES-28, MCP-1 -2518, and CCR5-59029 neither influenced the incidence of acute rejection nor affected long-term allograft survival upon liver transplantation in the context of this analysis.

Adult↗

PubMed2002

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.

Acute Disease↗