Polymorphisms of tumor necrosis factor and myeloperoxidase genes in patients with chronic renal failure on peritoneal dialysis.

Abstract

Background: Analyzing the molecular variants of immunological system genes helps to develop our understanding of the pathogenesis of several diseases. The tumor necrosis factor (TNF) is an important cytokine of cellular response and inflammation. The TNF gene is located within the MHC region on chromosome 6p21.3. Single nucleotide polymorphisms in the TNF gene, such as the one at a position -308, probably have a direct influence on TNF production. Myeloperoxidase, a heme enzyme, participates in micro-organism killing. The myeloperoxidase (MPO) gene is located on chromosome 17. In the promoter region, at position -463, G to A transition has been found, which causes decreased gene expression.

Aim: The aim of our study was to analyze the genetic polymorphisms of the TNF and MPO genes in patients with chronic renal failure.

Methods: The study included 95 patients with chronic renal failure and 115 healthy individuals. All participants were genotyped for TNF-308 and MPO promoter region polymorphisms by PCR, followed by digestion and gel electrophoresis. Genotype distribution was compared between patients and controls. For statistical analysis the Statistica PL 6.0 program was used. The Kruskal-Wallis and median test were employed; to evaluate relationship between quantitative data chi-square test was used.

Results: There were no significant differences in genotype distribution of TNF or MPO polymorphisms between patients and controls. Some differences may be associated with gender because the TNF1/TNF1 genotype was significantly more common in healthy women in comparison with women with chronic renal failure (p < 0.05). In men, no such differences were found. For MPO polymorphism, in men with renal failure the GG genotype was significantly more frequent than in healthy men (p < 0.05). Comparing the MPO genotype distribution in diabetic nephropathy patients and nondiabetic patients, we found a statistically significant difference: GG and AA genotypes were more frequent in diabetic nephropathy than in other renal diseases (73 versus 60% and 10.8 versus 1.7%, respectively; p < 0.05). The genotype distribution in patients with other renal diseases was similar to the control group. There was a correlation between the TNF genotype and the age of onset of glomerulonephritis. For myeloperoxidase, there was a significant association between genotype and the age of onset of renal disease. There was no relationship between the TNF and MPO genotypes and time to end-stage renal disease.

Conclusion: Our studies show that the TNF and MPO genes may play a role in chronic renal failure. The relationship observed between polymorphisms of the TNF and MPO genes and chronic renal failure may depend on the pathophysiological changes in different diseases underlying renal failure.