Interleukin-1 gene cluster polymorphisms predict risk 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).


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.
Wetmore
James B
JB
Department of Medicine, San Francisco VAMC/University of California, San Francisco, California 94121, USA. jwetmore@itsa.ucsf.edu
Hung
Adriana M
AM
Lovett
David H
DH
Sen
Saunak
S
Quershy
Omer
O
Johansen
Kirsten L
KL
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*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins