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Abstract

Cytokines and intercellular adhesive molecules (ICAM) play a crucial role in the pathogenesis of primary kidney disease and progression to end stage renal disease (ESRD). Cytokine secretion is reported to be dependent upon the SNP�s located in the cytokine genes. The role of different polymorphisms of cytokines and ICAM genes as a probable susceptibility factors for ESRD have been explored in the present study. The study was conducted on 258 ESRD patients and ethnically matched 569 controls. Individuals were genotyped for IL-6 (G174C), IL-4 (C590T), TNF-�± (-G308A and -G238A) and ICAM-1 (A469G) gene polymorphisms using standard PCR-RFLP based method. We observed significant difference in the genotype frequencies of the TNF-�± -308AA (p=0.001, OR=7.61, 95%CI=2.1-27.9), TNF-�± -238AA (p=0.001, OR=5.8, 95%CI=2.2�15.1). Further, C allele of IL-6 -G174C and G allele of ICAM-1 A469G were significantly different in ESRD patients when compared to controls (p=0.0001; OR=5.5, 95%CI=3.9-7.7 and p<0.0001; OR=3.8, 95%CI=3.1-4.7). For the IL-4 C590T polymorphism, though the homozygous mutant genotype (TT) was not found to be significantly associated with ESRD, a statistically significant association with T allele (p=0.0001) was found with the ESRD. Further, combined analysis revealed a higher risk in ESRD patients with low IL-4 and high IL-6 producing genotypes and high producing genotype of TNF-�± (308 and 238) with the increased risk of ~6.0 fold and 3.3 fold respectively. Our results suggest that IL-6, IL-4, TNF-�± and ICAM gene polymorphism may be risk factors for ESRD.

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