Effects of haplotypes in the interleukin 1β promoter on lipopolysaccharide-induced interleukin 1β expression

Previous studies have indicated that there are 3 common haplotypes composed of the -14702 -511, and ;-31 loci in the interleukin 1 beta (IL-1 beta) promoter in the Chinese population. The purpose of this study was to investigate the relationship between these haplotypes and lipopolysaccharide (LPS)-stimulated IL-1 beta expression by whole blood leukocytes in vitro and to evaluate the effects of these haplotypes on IL-1 beta gene transcription. Genomic DNAs were obtained from 105 healthy subjects. The genotypes at the 3 sites of the IL-1 beta promoter were determined by restriction fragment length polymorphism analysis. Haplotype frequency was evaluated by using the Arlequin software. Plasma IL-1 beta level was measured by enzyme-linked immunosorbent assay. The transcriptional activity of the haplotypes was determined by in vitro reporter gene. The results indicated that after the exposure to LIPS, whole blood leukocytes from subjects with the homozygous haplotype -1470G, -511C, and -31T (G-C-T) produced more IL-1 beta in vitro than those from subjects with haplotype -1470C, -511T, and -31C (C-T-C) and that the transcriptional activity of the haplotype G-C-T was also higher than that of the haplotype C-T-C. It is suggested that the haplotypes of the IL-1 beta promoter influence the expression and transcriptional activity of the IL-1 beta gene and that the upregulation of IL-1 beta gene expression after LIPS exposure in subjects with haplotype G-C-T may be due to an increased transcriptional activity of the haplotype.