Association of interleukin (IL)-4 intron-3 and IL-6 -174 G/C gene polymorphism with susceptibility to end-stage renal disease.
Earlier studies suggest that end-stage renal disease (ESRD) is associated with inflammatory state and have become a major cause of morbidity and mortality worldwide. This study speculated the role of interleukins (IL)-2, -4, and -6 cytokines gene polymorphism with risk of susceptibility to ESRD. Polymorphism in IL-2 (-330 T/G, polymerase chain reaction [PCR]-restriction fragment length polymorphism), IL-4 (intron-3, variable number of tandem repeat, variable number tandem repeats analysis), and IL-6 (-174 G/C, amplification refractory mutation system, i.e. ARMS-PCR) were genotyped in 193 ESRD patients and 180 controls. Significant difference was observed in genotype frequencies of IL-4 and IL-6 between ESRD patients and control group (p<0.001 and p=0.032, respectively). Patients had higher frequency of homozygous B2B2 genotype (IL-4) than controls (62.7% vs 46.7) and GG genotype of IL-6 (73.1% vs 60.6%). The genotypic frequencies of IL-2 were comparable in patients and controls (p=0.102). Significant association of IL-4 was also observed in patients with glomerulonephritis (p=0.001). Combination of low IL-4 and high IL-6 genotypes were significantly associated with ESRD showing the highest risk, i.e. >threefolds risk (odds ratio=3.48, 95%CI=1.88-6.42; p < 0.001) among the four possible combinations taking high IL-4 and low IL-6 as reference. Our study suggests that polymorphism in IL-4 and IL-6 may be associated with susceptibility to ESRD. Further, combined analysis implicated a higher risk in ESRD patients with low IL-4 and high IL-6 producing genotypes. This study provided the basis for defined anti-inflammatory approaches to limit renal disease progression.
Mittal
Rama Devi
RD
Department of Urology and Renal Transplantation, Sanjay Gandhi post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, India. ramamittal@yahoo.com
Manchanda
Parmeet Kaur
PK
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D007438:Introns; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
D017931:DNA Primers; C508598:IL4 protein, human; C508600:IL6 protein, human; D007376:Interleukin-2; D015850:Interleukin-6; D015847:Interleukin-4