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

Abstract

Objective. Significant variation in interleukin-1␤ (IL-1␤) protein secretion between subjects has been observed when using a lipopolysaccharide (LPS)/ATPmediated 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␤ protein secretion.Methods. The IL1B gene polymorphisms C؊511T, T؊31C, and C3954T were tested for association with LPS-induced secretion of IL-1␤ 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␤ 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␤ protein secretion.

Association of the interleukin‐1 gene cluster with radiographic signs of osteoarthritis of the hip

“…Several DNA variants within IL1B and IL1RN have been reported, including single-nucleotide polymorphisms (SNPs) in the promoter region (Ϫ511CϾT) and in exon 5 (3953CϾT) of IL1B and a variable-number tandem repeat (VNTR) of an 86-bp repeat in intron 2 of IL1RN. As reported by Hall et al (18), the rare Ϫ511T allele (allele 2 in our study) in the promoter region of IL1B altered an activator protein 2 promoter element. Moreover, the effect of the 3953CϾT and Ϫ511CϾT polymorphisms on the production of IL-1␤ protein was extensively studied, showing a haplotype containing the C at 3953 and the T at Ϫ511 that was associated with increased secretion of IL-1␤ after lipopolysaccharide (LPS) stimulation alone, in 2 independent study populations.…”

“…As reported by Hall et al (18), a haplotype carrying allele 2 of the Ϫ511 polymorphism in the promoter region of IL1B, together with allele 1 of 3953, was associated with increased secretion of IL-1␤ after stimulation of whole blood with LPS alone, in 2 independent study populations. Increased secretion of IL-1␤ may lead to a shift of the metabolic balance in cartilage in favor of matrix loss, which may ultimately result in OA.…”

“…For the IL1B Ϫ511 polymorphism, which was not measured by Moos et al (27), we observed a significant association between the occurrence of hip ROA and the rare allele that is associated with increased IL-1␤ secretion in ex vivo experiments (18). In the study by Loughlin et al (26), however, association with the Ϫ511 polymorphism was absent.…”

Interleukin-1β polymorphisms in Colombian patients with autoimmune rheumatic diseases

“…Our results are somehow different from those previously reported (Table 3). 6,16,21,[33][34][35][36][37] As stated by Hall et al 37 differences in assay methods, population origin and their health status, reagents, sample size, and monocyte numbers might all contribute to the differences observed among studies (Table 3). Our functional study was carried out in healthy homozygous individuals, who had not suffered from infection disease and were free of medication.…”

A meta-analysis of the association between CTLA-4 +49 A/G, −318 C/T, and IL-1 polymorphisms and susceptibility to cervical cancer

“…Therefore, increased levels of IL-1 may play a role in cervical cancer susceptibility. The IL-1 −511 C/T polymorphism has been found to be associated with increased intracellular IL-1B production [42]. IL-1RN regulates IL-1 activity by binding to the IL-1 receptor [43].…”