Tumor necrosis factor-alfa and monocyte chemoattractant protein-1 gene polymorphisms in kidney transplant recipients

Abstract

Tumor necrosis factor-alfa (TNF-α) gene polymorphism is supposed to have a significant influence on the incidence of acute rejection in renal transplantation. The monocyte chemoattractant protein-1 (MCP-1) is another factor supposed to modulate graft rejection. We studied TNF-α and MCP-1 gene polymorphisms in 84 kidney allograft recipients with polymerase chain reaction and restriction fragment length polymorphism and their serum levels by enzyme-linked immunosorbent assay. The patients were classified into two groups based on their outcomes: Group I (n = 47) recipients with stable graft function as the control group and group II (n=37) recipients who experienced acute graft rejection episodes in the first 30 days post-transplantation. A significantly higher incidence of TNF 2 /TNF 2 genotype was observed among patients with acute graft rejection in comparison with the control group (40.5% and 19.2% respectively, P <0.05), while no statistically significant differences were observed in the TNF 1 /TNF 1 genotype between the groups (59.4% and 80.8%, respectively, P >0.05). A significant elevation of serum TNF-α levels was found in group II than group I and between TNF 2 genotype compared with that of TNF1 genotype within group II recipients. Distribution of MCP-1 genotypes in patients with and without acute rejection episodes was not significantly different (70.2% and 76.6% for MCP-1 A/A and 29.7% and 23.4% for MCP-1 G/G, respectively, P >0.05). The serum MCP-1 levels were not significantly different between the groups and between MCP-1 G/G genotype and MCP-1 A/A genotype in group II recipients. In conclusion, TNF-α gene polymorphism or its serum levels may identify patients at risk of acute rejection, where patients with TNF 2 /TNF 2 genotype or high serum TNF-α levels are more likely to have acute rejection episodes, while there was no relation between MCP-1 genotype or its serum levels and acute rejection.

Monocyte chemoattractant protein-1 gene (MCP-1-2518 A/G) polymorphism and serological markers of hepatitis B virus infection in hemodialysis patients

“…The promoter region of the MCP-1 gene ( MCP1 ) was shown to influence MCP-1 expression [13,14]. The MCP1- 2518G allele was associated with up-regulation of both MCP-1 transcript and protein levels in many studies [11,13–16], but not all [17]. HD subjects with AG+GG genotypes of the MCP-1 gene ( MCP1 rs1024611) had higher MCP-1 levels than those with the AA variant [11]; this may predispose HD patients to HBV infection.…”

Changes of serum Amyloid-A (SAA), tumor necrosis factor-a (TNF-a), c-reactive protein (CRP) and association of CRP with cystatin-c in kidney transplantation

“…Tumor Necrosis Factor-a (TNF-a) is an endotoxin-induced glycoprotein, originally described as a circulating factor that can cause necrosis of tumor. However, accumulating evidence demonstrated that TNF-a is a key regulator of the inflammatory response and is implicated in the pathophysiological course of multiple disorders [14,15]. TNF-a, along with other pro-inflammatory cytokines (e.g., IL-6), are elevated in patients undergoing hemodialysis (HD).…”

“…In allograft rejection, activated immune cells involving macrophages, CD4+ T cells, natural killer (NK) cells, neutrophils, and endothelial cells have been shown to produce exaggerated amounts of TNF-a. Of note, combined serial assays of serum TNF-a and serum creatinine have greater predictive value than either test alone for the early diagnosis of acute rejection [2,14,15], while TNF-a gene polymorphisms may reveal a subgroup of graft recipients under an elevated risk of acute and delayed rejection [4]. Intriguingly, high TNF-a levels in donors may confer an additional risk for delayed graft rejection in kidney recipients.…”

“…In greater detail, high plasma (as well as urinary) concentrations of tumor necrosis factor -α (TNF-a, a pro-inflammatory cytokine) have been related to higher risk of graft rejection and impaired graft function, through activation of T lymphocytes [8][9][10][11]. Elevated serum amyloid A (SAA, an acute phase protein) has also exhibited an association with kidney allograft rejection [12][13][14][15][16][17], while increased C-reactive protein (CRP, an acute phase protein, as well) is also considered a harbinger of chronic allograft dysfunction, graft rejection and cardiovascular mortality [6,7,[17][18][19].…”