Correlation of polymorphic variation in the promoter region of the interleukin-1 beta gene with secretion of interleukin-1 beta protein.
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).


CONCLUSIONS
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.
Hall
Stephanie K
SK
Pfizer Global Research and Development, Groton, Connecticut 06340, USA.
Perregaux
David G
DG
Gabel
Christopher A
CA
Woodworth
Thasia
T
Durham
L Kathryn
LK
Huizinga
T W F
TW
Breedveld
F C
FC
Seymour
Albert B
AB
D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism*; D015810:Linkage Disequilibrium; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic / Q000235:genetics
D018501:Antirheumatic Agents; D007375:Interleukin-1; D008070:Lipopolysaccharides