糖尿性腎病變TNF-α 與IL-10 基因多型性之探討

Abstract

Diabetic nephropathy is a very common complication of diabetes mellitus. Mostly cytokines involved in these respective patients with hemodialysis are TNF-α, IL-2, IL-6 and IFN-γ. TNF-α mainly promotes the inflammation, induces apoptosis and regulates the secretions of other inflammatory mediators. MCP-1 is primarily produced by mesangial cells and tubular epithelial cells in kidney and mediates renal interstitial inflammation, tubular atrophy and interstitial fibrosis. IL-10 is an important component of the anti-inflammatory cytokine network in sepsis, suppressing gene expression and synthesis of proinflammatory cytokines. Gene polymorphisms of TNF-α and IL-10 are known to be related to the risk of death among patients with acute renal failure who require dialysis. The present study is to investigate the biochemistry parameter, gene polymorphisms of TNF-α -308 and IL-10 -1082, -819, -592 and their correlations to the protein expressions and blood and urine MCP-1 levels in subjects in diabetic nephropathy, diabetes mellitus and healthy groups. The results showed that heterozygotes of TNF-α -308, IL-10 -1082 and IL-10 -819 do not play a major role in the pathogenesis of diabetic nephropathy. The C/A heterozygotes of the IL-10 gene promoter at position -592 are the majority gene type of subjects in either diabetes mellitus or healthy group. However, prevalence of IL-10 -592 C/A, A/A and C/C respectively in 54.2%, 29.2% and 16.6% is found in subjects with diabetic nephropathy. In addition, blood levels of TNF-α, MCP-1 and TNF-α/IL-10 ratio and urine MCP-1 levels are significantly higher in the diabetic nephropathy than those in other groups; however, blood-MCP-1/TNF-αratio is significantly lower in subjects with diabetic nephropathy than those in other groups. Higher expressions of TNF-α, blood MCP-1 and urine MCP-1 are found in subjects with IL-10 -592 A/A homozygotes than those with other two genotypes in diabetic nephropathy group. Apparently, gene polymorphism of IL-10 -592 is closely related to cytokines associated to diabetic nephropathy.