Interleukin-1 gene cluster polymorphisms predict risk of ESRD.

Wetmore JB, Hung AM, Lovett DH, Sen S, Quershy O, Johansen KL
Kidney Int. 2005 68 (1): 278-84

PMID: 15954918 · DOI:10.1111/j.1523-1755.2005.00403.x

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.

MeSH Terms (16)

Aged Female Genetic Predisposition to Disease Genotype Humans Interleukin-1 Interleukin 1 Receptor Antagonist Protein Kidney Failure, Chronic Linkage Disequilibrium Male Middle Aged Multigene Family Polymorphism, Single Nucleotide Predictive Value of Tests Risk Factors Sialoglycoproteins

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