Abstract
Interleukin-1 beta (IL-1β) exerts a range of inflammatory and immunomodulatory activities that are important in host defense and autoimmune response. The IL-1β gene, located on chromosome 2 (2q13), is polymorphic. The influence of its polymorphism on 355 patients with autoimmune rheumatic diseases was examined. To this effect, 172 patients with rheumatoid arthritis (RA), 114 with systemic lupus erythematosus (SLE), and 69 with primary Sjögren's syndrome (pSS) were studied. The control group consisted of 392 matched healthy individuals. Genotyping of IL-1β single-nucleotide polymorphisms (SNPs) at positions −511 (C/T) and +3953 (C/T) was performed by the polymerase chain reaction-restriction fragment length polymorphism technique. In addition, levels of IL-1β were measured by immunoassay in supernatants of lipopolysaccharide (LPS)-stimulated and nonstimulated peripheral blood monocytes (PBM) obtained from 19 homozygous individuals for the three most common IL-1β likely haplotypes, all belonging to the control group. Allele+3953T was protective for SLE (odds ratio (OR)=0.57, 95% confidence intervals (CI)=0.34–0.88, P=0.01) as was the haplotype −511C+3953T (OR=0.43, 95%CI=0.25–0.74, pc=0.006). The latter was associated with a lower LPS-stimulated-PBM IL-1β secretion. Results suggest that IL-1β polymorphism influences the susceptibility to acquire SLE in our population. The protective association might be explained by the observed inhibitory effect of IL-1β +3953T allele on the secretion of IL-1β under inflammatory circumstances.
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 . The IL-1 family and inflammatory diseases. Clin Exp Rheumatol 2002; 20: S1–S13.
Dinarello CA . Biologic basis for interleukin-1 in disease. Blood 1996; 87: 2095–2147.
Nicklin MJ, Weith A, Duff GW . A physical map of the region encompassing the human interleukin-1 alpha, interleukin-1 beta and interleukin-1 receptor antagonist genes. Genomics 1994; 19: 382–384.
Di Giovine FS, Takhsh E, Blakemore AIF, Duff GW . Single base polymorphism at −511 in the human interleukin-1beta gene. Hum Mol Genet 1992; 1: 450.
Guash JF, Bertina RM, Reitsma PH . Five novel intragenic dimorphisms in the human interleukin-1 genes combine to high informativity. Cytokine 1996; 8: 598–602.
Pociot F, Molvig J, Wogensen L, Worsaae H, Nerup J . A TaqI polymorphism in the human interleukin-1beta secretion in vitro. Eur J Clin Invest 1992; 22: 396–402.
Dinarello CA, Sheldom MW . The role of interleukin-1 in disease. N Engl J Med 1993; 328: 106–113.
Pettipher ER, Higgs GA, Henderson B . Interleukin 1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint. Proc Natl Acad Sci USA 1986; 83: 8749–8753.
Joosten LAB, Helsen MMA, van de Loo FAJ, van den Berg WB . Anticytokine treatment of established type II collagen induced arthritis in DBA/1 mice: a comparative study using anti-TNFα, anti-IL-1α/β, and IL-1Ra. Arthritis Rheum 1996; 39: 797–809.
Chikanza IC, Kingsley G, Panayi GS . Peripheral blood and synovial fluid monocyte expression of interleukin-1α and interleukin-1β during active rheumatoid arthritis. J Rheumatol 1995; 22: 600–606.
Bresnihan B, Cobby M . Clinical and radiological effects of anakinra in patients with rheumatoid arthritis. Rheumatology 2003; 42 (Suppl 2): ii22–28.
Zoukhri D, Hodges RR, Byon D, Klubin CL . Role of proinflammatory cytokines in the impaired lacrimation associated with autoimmune xerophthalmia. Invest Ophthalmol Vis Sci 2002; 43: 1429–1436.
Yamakawa M, Weinstein R, Tsuji T, McBride J, Wong D, Login GR . Age-related alterations in IL-1β, TNFα, and IL-6 concentrations in parotid acinar cells from BALB/c and non-obese diabetic mice. J Histochem Cytochem 2000; 48: 1033–1041.
Boumba D, Skopouli FN, Moutsopoulos HM . Cytokine mRNA expression in the labial salivary gland tissues from patients with primary Sjögren's syndrome. Br J Rheumatol 1995; 34: 326–333.
Ogawa N, Dang H, Talal N . PCR analysis of cytokines produced in salivary glands of Sjögren's syndrome patients. In: Homma M, Sugai S, Tojo T, Miyasaka N, Akisuki M (eds). Sjögren's syndrome—State of the art, Proceedings of the Fourth International Symposium, Tokyo, Japan, 1993, pp 103–110. Kugler publications: Amsterdan/New York, 1994.
Willeke P, Schotte H, Schlüter B et al. Interleukin 1β and tumour necrosis factor α secreting cells are increased in the peripheral blood of patients with primary Sjögren's syndrome. Ann Rheum Dis 2003; 62: 359–362.
Jandl RC, George JL, Dinarello CA, Schur PH . The effect of interleukin 1 on IgG synthesis in systemic lupus erythematosus. Clin Immunol Immunopathol 1987; 45: 384–394.
Scuderi F, Convertino R, Molino N et al. Effect of pro-inflammatory/anti-inflammatory agents on cytokine secretion by peripheral blood mononuclear cells in rheumatoid arthritis and systemic lupus erythematosus. Autoimmunity 2003; 36: 71–77.
Sturfelt G, Roux-Lombard P, Wollheim FA, Dayer JM . Low levels of interleukin-1 receptor antagonist coincide with kidney involvement in systemic lupus erythematosus. Br J Rheumatol 1997; 36: 1283–1289.
Cox A, Camp NJ, Cannings C et al. Combined sib-TDT and TDT provide evidence for linkage of the interleukin-1 gene cluster to erosive rheumatoid arthritis. Hum Mol Genet 1999; 8: 1707–1713.
Buchs N, di Giovine FS, Silvestri T, Vannier E, Duff GW, Miossec P . IL-1B and IL-1Ra gene polymorphisms and disease severity in rheumatoid arthritis: interaction with their plasma levels. Genes Immun 2001; 2: 222–228.
Cantagrel A, Navaux F, Loubet-Lescoulie P et al. Interleukin-1 beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 gene polymorphisms: relationship to occurrence and severity of rheumatoid arthritis. Arthritis Rheum 1999; 42: 1093–1100.
Zhang X, Llamado L, Pillay I, Price P, Will R . Interleukin-1 gene polymorphism, disease activity and bone mineral metabolism in rheumatoid arthritis. Chin Med J 2002; 115: 46–49.
Cvetkovic JT, Wallberg-Jonsson S, Stegmayr B, Rantapaa-Dahlqvist S, Lefvert AK . Suceptibility for and clinical manifestations of rheumatoid arthritis are associated with polymorphisms of the TNF-alpha, IL-1beta, and IL-1Ra genes. J Rheumatol 2002; 29: 212–219.
Kaijzel EL, van Dongen H, Bakker AM, Breedveld FC, Huizinga TWJ, Verweij CL . Relationship of polymorphisms of the interleukin-1 gene cluster to occurrence and severity of rheumatoid arthritis. Tissue Antigens 2002; 59: 122–126.
Huang CM, Tsai FJ, Wu JY, Wu MC . Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in rheumatoid arthritis. Scand J Rheumatol 2001; 30: 225–228.
Genevay S, Di Giovine FS, Perneger TV et al. Association of interleukin-4 and interleukin-1B gene variants with Larsen score progression in rheumatoid arthritis. Arthritis Rheum 2002; 47: 303–309.
Huang CM, Wu MC, Wu JY, Tsai FJ . Lack of association of interleukin-1beta gene polymorphisms in Chinese patients with systemic lupus erythematosus. Rheumatol Int 2002; 21: 173–175.
Parks CG, Cooper GS, Dooley MA et al. Systemic lupus erythematosus and genetic variation in the intreleukin 1 gene cluster: a population based study in the southeastern United States. Ann Rheum Dis 2004; 63: 91–94.
Hulkkonen J, Pertovaara M, Antonen J, Pasternack A, Hurme M . IL-1 gene family haplotypes and Raynaud's phenomenon in primary Sjogren' syndrome. Rheumatology 2002; 41: 1206–1208 (letter).
Muraki Y, Tsutsumi A, Takahashi R et al. Polymorphisms of the IL-1β gene in Japanese patients with Sjögren's syndrome and systemic lupus erythematosus. J Rheumatol 2004; 31: 720–725.
Correa PA, Whitworth WC, Kuffner T, McNicholl J, Anaya JM . HLA-DR and DQB1 gene polymorphism in the North-western Colombian population. Tissue Antigens 2002; 59: 436–439.
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.
Dorffel Y, Latsch C, Stuhlmuller B et al. Preactivated peripheral blood monocytes in patients with essential hypertension. Hypertension 1999; 34: 113–117.
Hefler LA, Tempfer CB, Unfried G et al. A polymorphism of the interleukin-1beta gene and idiopathic recurrent miscarriage. Fertil Steril 2001; 76: 377–379.
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.
Hall SK, Perregaux DG, Gabel CA et al. Correlation of polymorphic variation in the promoter region of the interleukin-1 beta gene with secretion of interleukin-1 beta protein. Arthritis Rheum 2004; 50: 1976–1983.
Anaya JM, Correa PA, Mantilla RD, Arcos-Burgos M . Rheumatoid arthritis association in Colombian population is restricted to HLA-DRB1*04 QRRAA alleles. Genes Immun 2002; 3: 56–58.
Anaya JM, Correa PA, Mantilla RD, Arcos-Burgos M . TAP, HLA-DQB1 and HLA-DRB1 polymorphisms in Colombian patients with primary Sjögren's syndrome. Semin Arthritis Rheum 2002; 31: 296–305.
Anaya JM, Uribe M, Pérez A et al. Clinical and immunological factors associated with lupus nephritis in northwestern Colombian patients. Biomedica 2003; 23: 293–300.
Arnett FC, Edworthy SM, Bloch DA, McShane PJ, Fries JF, Cooper NS . The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315–324.
Tan EM, Cohen AS, Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.
Vitali C, Bombardieri S, Jonsson R et al. Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus group. Ann Rheum Dis 2002; 61: 554–558.
Schneider S, Roessli D, Excoffier L. Arlequin: software for population genetics data analysis. Ver 2000. Genetics and Biometry Lab, Department of Anthropology, University of Geneva, 2000.
Acknowledgements
We thank all the patients and participants of this study, and S Ahuja (UTHSCSA) for his valuable support. We also thank the two anonymous reviewers of this paper for their important comments. This work was supported by Asociación Colombiana de Reumatologia, and Fundación para la promoción de la Investigación y Tecnologia, Bogotá, Colombia.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Camargo, J., Correa, P., Castiblanco, J. et al. Interleukin-1β polymorphisms in Colombian patients with autoimmune rheumatic diseases. Genes Immun 5, 609–614 (2004). https://doi.org/10.1038/sj.gene.6364133
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gene.6364133
Keywords
This article is cited by
-
Differential expression of the inflammasome complex genes in systemic lupus erythematosus
Immunogenetics (2020)
-
Pro-inflammatory cytokine response pre-dominates immuno-genetic pathway in development of rheumatoid arthritis
Molecular Biology Reports (2020)
-
Polymorphisms of cytokine genes and tuberculosis in two independent studies
Scientific Reports (2019)
-
Variants in LTA, TNF, IL1B and IL10 genes associated with the clinical course of sepsis
Immunologic Research (2016)
-
Interleukin-1 β gene polymorphisms in Egyptian patients with rheumatoid arthritis
Comparative Clinical Pathology (2014)