title: Interleukin-1 gene cluster polymorphisms predict risk of ESRD.
abstract: 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).
  
  
  CONCLUSIONS
  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.affiliation: Department of Medicine, San Francisco VAMC/University of California, San Francisco, California 94121, USA. jwetmore@itsa.ucsf.edu
authors.forename: James B
authors.initials: JB
authors.lastname: Wetmore
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Hung
authors.forename: David H
authors.initials: DH
authors.lastname: Lovett
authors.forename: Saunak
authors.initials: S
authors.lastname: Sen
authors.forename: Omer
authors.initials: O
authors.lastname: Quershy
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: Johansen
mesh_terms: D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000453:epidemiology* / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012307:Risk Factors; D012795:Sialoglycoproteins / Q000235:genetics*
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins