Correlation of polymorphic variation in the promoter region of the IL-1 beta gene with secretion of IL-1 beta protein

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Arthritis Rheum. 2004 Jun;50(6):1976-83.

Correlation of polymorphic variation in the promoter region of the

interleukin-1 beta gene with secretion of interleukin-1 beta protein.

Hall SK, Perregaux DG, Gabel CA, Woodworth T, Durham LK, Huizinga TW,

Breedveld FC, Seymour AB.

Pfizer Global Research and Development, Groton, Connecticut 06340, USA.

OBJECTIVE: Significant variation in interleukin-1 beta (IL-1 beta)

protein secretion between subjects has been observed when using a

lipopolysaccharide (LPS)/ATP-mediated ex vivo blood stimulation assay.

To explore the potential relationships between genetic polymorphisms in

the IL1B cytokine gene and cellular responses to inflammatory stimuli

such as LPS, we investigated the hypothesis that polymorphisms within

the promoter and exon 5 of the IL1B gene contribute to the observed

differences in IL-1 beta protein secretion. METHODS: The IL1B gene

polymorphisms C-511T, T-31C, and C3954T were tested for association with

LPS-induced secretion of IL-1 beta protein as measured by an ex vivo

blood stimulation assay. Samples from 2 independent study populations (n

= 31 and n = 25) were available for use in the ex vivo assay after

consent was obtained to analyze the DNA. RESULTS: A specific haplotype,

composed of the T allele at -511 and the C allele at -31, was

significantly associated with a 2-3-fold increase in LPS-induced IL-1

beta protein secretion. This association was observed in both of the

independent study populations (P = 0.0084 and P = 0.0017).

CONCLUSION: These data suggest that polymorphisms within the promoter

region of the IL1B gene contribute to observed differences in

LPS-induced IL-1 beta protein secretion.

PMID: 15188375

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