Abstract
Since the effect of IL1B polymorphisms on IL-1β production is still controversial, we selected two polymorphisms to test their cis-acting effect on IL-1β mRNA expression by means of the allele-specific transcript quantification and the haplotype analysis. As for the C−31T polymorphism, we found that expression of the −31T allele was 2.2 times of the −31C allele. This higher transcription efficiency may correspond to the fact that C−31T is located in a TATA box. The other polymorphism, C+3954T, did not alter the levels of transcription. The use of the allele-specific transcript quantification enables us to exclude trans-acting effects of polymorphisms on the gene expression and contributes to understanding the roles of the IL1B polymorphisms in susceptibility to multifactorial diseases.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 6 digital issues and online access to articles
$119.00 per year
only $19.83 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Dinarello CA . Biologic basis for interleukin-1 in disease. Blood 1996; 87: 2095–2147.
Kornman KS, Crane A, Wang HY et al. The interleukin-1 genotype as a severity factor in adult periodontal disease. J Clin Periodontol 1997; 24: 72–77.
Du Y, Dodel RC, Eastwood BJ et al. Association of an interleukin 1 alpha polymorphism with Alzheimer's disease. Neurology 2000; 55: 480–483.
Bensen JT, Langefeld CD, Hawkins GA et al. Nucleotide variation, haplotype structure, and association with end-stage renal disease of the human interleukin-1 gene cluster. Genomics 2003; 82: 194–217.
Langdahl BL, Lokke E, Carstens M, Stenkjaer LL, Eriksen EF . Osteoporotic fractures are associated with an 86-base pair repeat polymorphism in the interleukin-1—receptor antagonist gene but not with polymorphisms in the interleukin-1beta gene. J Bone Miner Res 2000; 15: 402–414.
El-Omar EM, Carrington M, Chow WH et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 2000; 404: 398–402.
Hamajima N, Matsuo K, Saito T et al. Interleukin 1 polymorphisms, lifestyle factors, and Helicobacter pylori infection. Jpn J Cancer Res 2001; 92: 383–389.
Santtila S, Savinainen K, Hurme M . Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol 1998; 47: 195–198.
Hwang IR, Kodama T, Kikuchi S et al. Effect of interleukin 1 polymorphisms on gastric mucosal interleukin 1beta production in Helicobacter pylori infection. Gastroenterology 2002; 123: 1793–1803.
Kaijzel EL, Bayley J-P, van Krugten MV et al. Allele-specific quantification of tumor necrosis factor alpha (TNF) transcription and the role of promoter polymorphisms in rheumatoid arthritis patients and healthy individuals. Genes Immun 2001; 2: 135–144.
Hulkkonen J, Laippala P, Hurme M . A rare allele combination of the interleukin-1 gene complex is associated with high interleukin-1 beta plasma levels in healthy individuals. Eur Cytokine Network 2000; 11: 251–255.
Pociot F, Molvig J, Wogensen L, Worsaae H, Nerup J . A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. Eur J Clin Invest 1992; 22: 396–402.
Hernandez-Guerrero C, Monzon-Bordonaba F, Jimenez-Zamudio L et al. In-vitro secretion of proinflammatory cytokines by human amniochorion carrying hyper-responsive gene polymorphisms of tumour necrosis factor-alpha and interleukin-1beta. Mol Hum Reprod 2003; 9: 625–629.
Dominici R, Malferrari G, Mariani C, Grimaldi L, Biunno I . The interleukin 1-beta exonic (+3953) polymorphism does not alter in vitro protein secretion. Exp Mol Pathol 2002; 73: 139–141.
Cox A, Camp NJ, Nicklin MJ, di Giovine FS, Duff GW . An analysis of linkage disequilibrium in the interleukin-1 gene cluster, using a novel grouping method for multiallelic markers. Am J Hum Genet 1998; 62: 1180–1188.
Hurme M, Santtila S . IL-1 receptor antagonist (IL-1Ra) plasma levels are co-ordinately regulated by both IL-1Ra and IL-1beta genes. Eur J Immunol 1998; 28: 2598–2602.
Vamvakopoulos J, Green C, Metcalfe S . Genetic control of IL-1beta bioactivity through differential regulation of the IL-1 receptor antagonist. Eur J Immunol 2002; 32: 2988–2996.
Kimura R, Nishioka T, Ishida T . The SDF1-G801A polymorphism is not associated with SDF1 gene expression in Epstein–Barr virus-transformed lymphoblastoid cells. Genes Immun 2003; 4: 356–361.
Nemetz A, Toth M, Garcia-Gonzalez MA et al. Allelic variation at the interleukin 1beta gene is associated with decreased bone mass in patients with inflammatory bowel diseases. Gut 2001; 49: 644–649.
Wang ZC, Yunis EJ, De los Santos MJ, Xiao L, Anderson DJ, Hill JA . T helper 1-type immunity to trophoblast antigens in women with a history of recurrent pregnancy loss is associated with polymorphism of the IL1B promoter region. Genes Immun 2002; 3: 38–42.
Wang Y, Kato N, Hoshida Y et al. Interleukin-1beta gene polymorphisms associated with hepatocellular carcinoma in hepatitis C virus infection. Hepatology 2003; 37: 65–71.
Ito LS, Iwata H, Hamajima N et al. Significant reduction in breast cancer risk for Japanese women with interleukin 1B −31 CT/TT relative to CC genotype. Jpn J Clin Oncol 2002; 32: 398–402.
Bidwell J, Keen L, Gallagher G et al. Cytokine gene polymorphism in human disease: on-line databases. Genes Immun 1999; 1: 3–19.
Bidwell J, Keen L, Gallagher G et al. Cytokine gene polymorphism in human disease: on-line databases, supplement 1. Genes Immun 2001; 2: 61–70.
Haukim N, Bidwell JL, Smith AJ et al. Cytokine gene polymorphism in human disease: on-line databases, supplement 2. Genes Immun 2002; 3: 313–330.
Acknowledgements
We are grateful to Dr M Hirai, Tokyo Women's Medical University, for providing DNA samples. This work was partly supported by the Japan Society for Promotion of Science and Ministry of Education, Culture, Sports, Science and Technology, Japan. This study constitutes a part of doctorial dissertation (RK) submitted to the University of Tokyo.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kimura, R., Nishioka, T., Soemantri, A. et al. Cis-acting effect of the IL1B C−31T polymorphism on IL-1β mRNA expression. Genes Immun 5, 572–575 (2004). https://doi.org/10.1038/sj.gene.6364128
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gene.6364128
Keywords
This article is cited by
-
Ancestry informative markers and selected single nucleotide polymorphisms in immunoregulatory genes on preterm labor and preterm premature rupture of membranes: a case control study
BMC Pregnancy and Childbirth (2016)
-
Gene Variant and Level of IL-1β in Ischemic Stroke Patients With and Without Type 2 Diabetes Mellitus
Journal of Molecular Neuroscience (2015)
-
Significance of IL-1RA Polymorphism in Iranian Patients with Inflammatory Bowel Disease
Digestive Diseases and Sciences (2015)
-
Association of Innate Immune Single-Nucleotide Polymorphisms with the Electroencephalogram During Desflurane General Anaesthesia
Journal of Molecular Neuroscience (2014)
-
Interleukin-1beta Promoter (−31T/C and −511C/T) Polymorphisms in Major Recurrent Depression
Journal of Molecular Neuroscience (2011)