Abstract
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-gamma (IFN-gamma) plays an important pathogenetic role in several inflammatory diseases. We have explored the role of MIF -173 G/C, INF-gamma +874 A/T and INF-gamma CA repeat microsatellite gene polymorphisms as a susceptibility for ESRD. We genotyped MIF and IFN-gamma 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. 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-gamma +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-gamma CA microsatellite polymorphism (p=0.0001) (CA(17))/(CA(17)). Combined analysis revealed a higher risk ( approximately 9-fold) in ESRD patients with high MIF -173 G/C and high INF-gamma +874 A/T protein producing phenotypes. These results highlight the role of MIF and IFN-gamma in ESRD disease.
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