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Correlation of polymorphic variation in the promoter region of the interleukin-1β gene with secretion of interleukin-1β protein

✍ Scribed by Stephanie K. Hall; David G. Perregaux; Christopher A. Gabel; Thasia Woodworth; L. Kathryn Durham; T. W. F. Huizinga; F. C. Breedveld; Albert B. Seymour

Publisher
John Wiley and Sons
Year
2004
Tongue
English
Weight
91 KB
Volume
50
Category
Article
ISSN
0004-3591

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✦ Synopsis

Abstract

Objective

Significant variation in interleukin‐1β (IL‐1β) 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‐1β protein secretion.

Methods

The IL1B gene polymorphisms C−511T, T−31C, and C3954T were tested for association with LPS‐induced secretion of IL‐1β 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‐1β 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‐1β protein secretion.

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