Association of proinflammatory cytokines with end stage renal disease

Context: Cytokines play an important role in the pathogenesis of kidney disease and its progression to ESRD. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is released by macrophages and lymphocytes and interferon-γ (IFN-γ) plays an important pathogenetic role in several inflammatory diseases. Objectives: We have explored the role of MIF −173 G/C, INF-γ +874 A/T and INF-γ CA repeat microsatellite gene polymorphisms as a susceptibility for ESRD. Participants and methods: We genotyped MIF and IFN-γ gene polymorphisms in 258 patients with ESRD and 569 healthy controls free of any renal disease using PCR–RFLP, gene sequencing and gene scanning methods. Results: The frequency of high producer MIF −173 CC genotype was higher (10.1%) in ESRD than in controls (1.2%) (p = 0.0001, OR = 8.9; 95%CI = 3.8–21.0). It was observed that there was significant differences in the genotype frequencies of the IFN-γ +874 A/T at genotypic as well as at allelic level (p = 0.0023 and p = 0.001) among patients and controls. A significant difference was found in the frequency distribution between the two groups at IFN-γ CA microsatellite polymorphism (p = 0.0001) (CA17)/(CA17). Combined analysis revealed a higher risk (∼9-fold) in ESRD patients with high MIF −173 G/C and high INF-γ +874 A/T protein producing phenotypes. Conclusions: These results highlight the role of MIF and IFN-γ in ESRD disease.