title: Association of interleukin (IL)-4 intron-3 and IL-6 -174 G/C gene polymorphism with susceptibility to end-stage renal disease.
abstract: 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.
authors.affiliation: Department of Urology and Renal Transplantation, Sanjay Gandhi post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, India. ramamittal@yahoo.com
authors.forename: Rama Devi
authors.initials: RD
authors.lastname: Mittal
authors.forename: Parmeet Kaur
authors.initials: PK
authors.lastname: Manchanda
mesh_terms: 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
chemical_list: D017931:DNA Primers; C508598:IL4 protein, human; C508600:IL6 protein, human; D007376:Interleukin-2; D015850:Interleukin-6; D015847:Interleukin-4