BACKGROUND: Patients with chronic kidney disease manifest an inflammatory state relative to healthy individuals. Inflammation is regulated in part by genes of the interleukin-1 (IL-1) gene cluster. We hypothesized that polymorphisms in this gene cluster may be associated with risk of end-stage renal disease (ESRD). METHODS: Polymorphisms in the IL-1 gene cluster were examined in a cohort of 239 racially diverse hemodialysis (HD) patients and 252 controls. These individuals were genotyped for 3 single nucleotide polymorphisms (SNPs) in the IL-1alpha and beta genes, and a variable-number-of-tandem-repeats polymorphism in the IL-1 receptor antagonist gene (IL-1RN). Polymorphisms were analyzed by logistic regression for their independent associations with ESRD, and the effect of allele dose of IL-1RN on risk for ESRD was examined. The interaction between race and genotype was also investigated. RESULTS: A logistic regression model demonstrated that homozygosity for allele 2 of the IL-1RN variable-number-of-tandem-repeats (VNTR) polymorphism was associated with ESRD independent of race (P < 0.0005). The IL-1alpha-889 promoter SNP was associated with ESRD independent of race and of the IL-1RN polymorphism (P= 0.04). The IL-1beta-511 promoter SNP is associated with ESRD, but this is accounted for by race (P= 0.04). CONCLUSION: Two polymorphisms within the IL-1 gene cluster are associated with ESRD independent of race. This finding is one of the strongest associations between genotype and ESRD reported, and suggests that polymorphisms in the IL-1 gene cluster affect the risk of development of ESRD.
BACKGROUND:Patients with chronic kidney disease manifest an inflammatory state relative to healthy individuals. Inflammation is regulated in part by genes of the interleukin-1 (IL-1) gene cluster. We hypothesized that polymorphisms in this gene cluster may be associated with risk of end-stage renal disease (ESRD). METHODS: Polymorphisms in the IL-1 gene cluster were examined in a cohort of 239 racially diverse hemodialysis (HD) patients and 252 controls. These individuals were genotyped for 3 single nucleotide polymorphisms (SNPs) in the IL-1alpha and beta genes, and a variable-number-of-tandem-repeats polymorphism in the IL-1 receptor antagonist gene (IL-1RN). Polymorphisms were analyzed by logistic regression for their independent associations with ESRD, and the effect of allele dose of IL-1RN on risk for ESRD was examined. The interaction between race and genotype was also investigated. RESULTS: A logistic regression model demonstrated that homozygosity for allele 2 of the IL-1RN variable-number-of-tandem-repeats (VNTR) polymorphism was associated with ESRD independent of race (P < 0.0005). The IL-1alpha-889 promoter SNP was associated with ESRD independent of race and of the IL-1RN polymorphism (P= 0.04). The IL-1beta-511 promoter SNP is associated with ESRD, but this is accounted for by race (P= 0.04). CONCLUSION: Two polymorphisms within the IL-1 gene cluster are associated with ESRD independent of race. This finding is one of the strongest associations between genotype and ESRD reported, and suggests that polymorphisms in the IL-1 gene cluster affect the risk of development of ESRD.
Authors: Irina A Leaf; Shunsaku Nakagawa; Bryce G Johnson; Jin Joo Cha; Kristen Mittelsteadt; Kevin M Guckian; Ivan G Gomez; William A Altemeier; Jeremy S Duffield Journal: J Clin Invest Date: 2016-11-21 Impact factor: 14.808
Authors: James B Wetmore; David H Lovett; Adriana M Hung; Galen Cook-Wiens; Jonathan D Mahnken; Saunak Sen; Kirsten L Johansen Journal: Nephrology (Carlton) Date: 2008-09-25 Impact factor: 2.506
Authors: Erika I Boesen; Jennifer M Sasser; Mohamed A Saleh; William A Potter; Mandy Woods; Timothy D Warner; Jennifer S Pollock; David M Pollock Journal: Am J Physiol Renal Physiol Date: 2008-06-04
Authors: A M Matteini; J Li; E M Lange; T Tanaka; L A Lange; R P Tracy; Y Wang; M L Biggs; D E Arking; M D Fallin; A Chakravarti; B M Psaty; S Bandinelli; L Ferrucci; A P Reiner; J D Walston Journal: Cytokine Date: 2013-10-29 Impact factor: 3.861