A Taql polymorphism in the human interleukin‐1β (IL‐1β) gene correlates with IL‐1β secretion in vitro

Abstract

In the present study we searched for restriction fragment length polymorphisms (RFLP) in the human interleukin-1 beta (IL-1 beta) gene and for correlations to monocyte (Mo) function in non-related healthy donors and insulin-dependent diabetic patients. We demonstrated a diallelic polymorphism with the restriction enzyme TaqI consisting of fragments of 9.4 kb and 13.4 kb. No differences in allele or genotype frequencies of this RFLP were observed between randomly selected controls and randomly selected patients with insulin-dependent diabetes mellitus (IDDM). However, when analysing IDDM patients negative for HLA-DR3 and -DR4, our data demonstrate that the 13.4 kb allele is more frequent in this group compared to a matched control group. The functional impact of this RFLP was studied by analysing in vitro stimulated Mo IL-1 beta response. An IL-1 beta allele dosage effect on secretory capacity was observed after LPS-stimulation: 13.4/13.4 kb homozygous individuals secreted significantly more IL-1 beta than 9.4/13.4 kb heterozygous individuals, who secreted significantly more than 9.4/9.4 kb homozygous individuals. Analyses of supernatants from LPS-stimulated Mo cultures from individuals with each TaqI IL-1 beta genotype revealed no differences in the mouse thymocyte co-stimulatory assay when compared on a molar basis, indicating that the TaqI polymorphism gave rise only to quantitative differences in expression levels and probably not to a mutant IL-1 beta.(ABSTRACT TRUNCATED AT 250 WORDS)

Multi-locus interactions predict risk for post-PTCA restenosis: an approach to the genetic analysis of common complex disease

“…[15][16][17][18][19][20][21][22][23][24][25][26][27][28] To confirm genotype assignments, the PCR procedure was performed in replicate on all samples. Scoring was carried out by two independent observers.…”

Evaluation of TNF-α and IL-1β polymorphisms in Taiwan Chinese patients with pterygium

“…Different polymorphisms have been described in the IL-1b gene and at least two of them could influence the protein production: one located in the promoter region at position À511, 19 and the other in exon 5. 20 Moreover, the action of IL-1b is regulated by its naturally occurring inhibitor IL-1Ra. 19,20 IL-1Ra has five polymorphic site variable number tandem repeats in intron 2 and 4 SNPs, including one in exon 2.…”

“…20 Moreover, the action of IL-1b is regulated by its naturally occurring inhibitor IL-1Ra. 19,20 IL-1Ra has five polymorphic site variable number tandem repeats in intron 2 and 4 SNPs, including one in exon 2. These IL1Ra gene polymorphisms have been associated with altered production rates of IL-1Ra protein.…”

“…The polymorphism was analysed by PCR amplification followed by restriction analysis. 9,19,20 The PCR products from the same individual were mixed together and 10 ml of this solution was loaded into 3% agarose gel containing ethidium bromide for electrophoresis.…”

“…In this study, TNF-a-308 promoter, IL-1b-511 promoter, IL-1b exon 5, and IL-1 receptor antagonist (IL-1 Ra), which had been reported to be associated with elevated TNF and IL-1b levels, [9][10][11]19,20 were evaluated in order to understand whether these polymorphisms are associated with increased susceptibility for pterygium.…”