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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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