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. 1995 Nov;102(2):379–383. doi: 10.1111/j.1365-2249.1995.tb03793.x

Allelic polymorphism in IL-1 beta and IL-1 receptor antagonist (IL-1Ra) genes in inflammatory bowel disease.

G Bioque 1, J B Crusius 1, I Koutroubakis 1, G Bouma 1, P J Kostense 1, S G Meuwissen 1, A S Peña 1
PMCID: PMC1553429  PMID: 7586694

Abstract

Recent reports have shown that allele 2 of the IL-1 receptor antagonist (IL-1Ra) gene is over-represented in ulcerative colitis (UC). Healthy individuals carrying allele 2 of this gene have increased production of IL-1Ra protein. Since the final outcome of the biological effects of IL-1 beta may depend on the relative proportion of these two cytokines, we have studied if a TaqI polymorphism in the IL-1 beta gene, which is relevant to IL-1 beta protein production, may be involved in the genetic susceptibility to UC and Crohn's disease (CD), in association with the established IL-1Ra gene polymorphism. Polymorphisms in the closely linked genes for IL-1 beta and IL-1Ra were typed in 100 unrelated Dutch patients with UC, 79 with CD, and 71 healthy controls. The polymorphic regions in exon 5 of the IL-1 beta gene and in intron 2 of the IL-1Ra gene, were studied by polymerase chain reaction (PCR)-based methods. The IL-1 beta allele frequencies in UC and CD patients did not differ from those in healthy controls. In order to study if the IL-1 beta gene polymorphism might participate synergistically with the IL-1Ra gene polymorphism in susceptibility to UC and CD, individuals were distributed into carriers and non-carriers of allele 2 of the genes encoding IL-1 beta and IL-1Ra, in each of the patient groups and controls. Results indicated a significant association of this pair of genes, estimated by the odds ratio (OR) after performing Fisher's exact test, in the UC group (P = 0.023, OR = 2.81), as well as in the CD group (P = 0.01, OR = 3.79). Thus, non-carriers of IL-1 beta allele 2 were more often present in the subgroup of patients carrying the IL-1Ra allele 2. By contrast, no association of these alleles was detected in the group of healthy controls (P = 1.00, OR = 0.92). These results suggest that the IL-1 beta/IL-1Ra allelic cluster may participate in defining the biological basis of predisposition to chronic inflammatory bowel diseases.

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Selected References

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  1. Bailly S., di Giovine F. S., Duff G. W. Polymorphic tandem repeat region in interleukin-1 alpha intron 6. Hum Genet. 1993 Mar;91(1):85–86. doi: 10.1007/BF00230231. [DOI] [PubMed] [Google Scholar]
  2. Bell A. L., Markey G. M., Alexander H. D., Morris T. C., McMillan S. A., McNally J. A. Myeloperoxidase deficiency in a patient with rheumatoid arthritis: oxygenation and radical activity by phagocytic cells. Br J Rheumatol. 1993 Feb;32(2):162–165. doi: 10.1093/rheumatology/32.2.162. [DOI] [PubMed] [Google Scholar]
  3. Cominelli F., Nast C. C., Clark B. D., Schindler R., Lierena R., Eysselein V. E., Thompson R. C., Dinarello C. A. Interleukin 1 (IL-1) gene expression, synthesis, and effect of specific IL-1 receptor blockade in rabbit immune complex colitis. J Clin Invest. 1990 Sep;86(3):972–980. doi: 10.1172/JCI114799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Danis V. A., Millington M., Hyland V. J., Grennan D. Cytokine production by normal human monocytes: inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism. Clin Exp Immunol. 1995 Feb;99(2):303–310. doi: 10.1111/j.1365-2249.1995.tb05549.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dinarello C. A. Biology of interleukin 1. FASEB J. 1988 Feb;2(2):108–115. [PubMed] [Google Scholar]
  6. Duerr R. H., Neigut D. A. Molecularly defined HLA-DR2 alleles in ulcerative colitis and an antineutrophil cytoplasmic antibody-positive subgroup. Gastroenterology. 1995 Feb;108(2):423–427. doi: 10.1016/0016-5085(95)90069-1. [DOI] [PubMed] [Google Scholar]
  7. Endres S., Cannon J. G., Ghorbani R., Dempsey R. A., Sisson S. D., Lonnemann G., Van der Meer J. W., Wolff S. M., Dinarello C. A. In vitro production of IL 1 beta, IL 1 alpha, TNF and IL2 in healthy subjects: distribution, effect of cyclooxygenase inhibition and evidence of independent gene regulation. Eur J Immunol. 1989 Dec;19(12):2327–2333. doi: 10.1002/eji.1830191222. [DOI] [PubMed] [Google Scholar]
  8. Isaacs K. L., Sartor R. B., Haskill S. Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification. Gastroenterology. 1992 Nov;103(5):1587–1595. doi: 10.1016/0016-5085(92)91182-4. [DOI] [PubMed] [Google Scholar]
  9. Lennard-Jones J. E. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl. 1989;170:2–19. doi: 10.3109/00365528909091339. [DOI] [PubMed] [Google Scholar]
  10. Ligumsky M., Simon P. L., Karmeli F., Rachmilewitz D. Role of interleukin 1 in inflammatory bowel disease--enhanced production during active disease. Gut. 1990 Jun;31(6):686–689. doi: 10.1136/gut.31.6.686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mahida Y. R., Lamming C. E., Gallagher A., Hawthorne A. B., Hawkey C. J. 5-Aminosalicylic acid is a potent inhibitor of interleukin 1 beta production in organ culture of colonic biopsy specimens from patients with inflammatory bowel disease. Gut. 1991 Jan;32(1):50–54. doi: 10.1136/gut.32.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mahida Y. R., Wu K., Jewell D. P. Enhanced production of interleukin 1-beta by mononuclear cells isolated from mucosa with active ulcerative colitis of Crohn's disease. Gut. 1989 Jun;30(6):835–838. doi: 10.1136/gut.30.6.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mansfield J. C., Holden H., Tarlow J. K., Di Giovine F. S., McDowell T. L., Wilson A. G., Holdsworth C. D., Duff G. W. Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist. Gastroenterology. 1994 Mar;106(3):637–642. doi: 10.1016/0016-5085(94)90696-3. [DOI] [PubMed] [Google Scholar]
  14. Mølvig J., Baek L., Christensen P., Manogue K. R., Vlassara H., Platz P., Nielsen L. S., Svejgaard A., Nerup J. Endotoxin-stimulated human monocyte secretion of interleukin 1, tumour necrosis factor alpha, and prostaglandin E2 shows stable interindividual differences. Scand J Immunol. 1988 Jun;27(6):705–716. doi: 10.1111/j.1365-3083.1988.tb02404.x. [DOI] [PubMed] [Google Scholar]
  15. Nakamura M., Saito H., Kasanuki J., Tamura Y., Yoshida S. Cytokine production in patients with inflammatory bowel disease. Gut. 1992 Jul;33(7):933–937. doi: 10.1136/gut.33.7.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nicklin M. J., Weith A., Duff G. W. A physical map of the region encompassing the human interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes. Genomics. 1994 Jan 15;19(2):382–384. doi: 10.1006/geno.1994.1076. [DOI] [PubMed] [Google Scholar]
  17. Pociot F., Mølvig 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 Jun;22(6):396–402. doi: 10.1111/j.1365-2362.1992.tb01480.x. [DOI] [PubMed] [Google Scholar]
  18. Rachmilewitz D., Simon P. L., Schwartz L. W., Griswold D. E., Fondacaro J. D., Wasserman M. A. Inflammatory mediators of experimental colitis in rats. Gastroenterology. 1989 Aug;97(2):326–337. doi: 10.1016/0016-5085(89)90068-1. [DOI] [PubMed] [Google Scholar]
  19. Reinecker H. C., Steffen M., Witthoeft T., Pflueger I., Schreiber S., MacDermott R. P., Raedler A. Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease. Clin Exp Immunol. 1993 Oct;94(1):174–181. doi: 10.1111/j.1365-2249.1993.tb05997.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Satsangi J., Jewell D. P., Rosenberg W. M., Bell J. I. Genetics of inflammatory bowel disease. Gut. 1994 May;35(5):696–700. doi: 10.1136/gut.35.5.696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Theofilopoulos A. N. The basis of autoimmunity: Part II. Genetic predisposition. Immunol Today. 1995 Mar;16(3):150–159. doi: 10.1016/0167-5699(95)80133-2. [DOI] [PubMed] [Google Scholar]
  22. Toyoda H., Wang S. J., Yang H. Y., Redford A., Magalong D., Tyan D., McElree C. K., Pressman S. R., Shanahan F., Targan S. R. Distinct associations of HLA class II genes with inflammatory bowel disease. Gastroenterology. 1993 Mar;104(3):741–748. doi: 10.1016/0016-5085(93)91009-7. [DOI] [PubMed] [Google Scholar]
  23. di Giovine F. S., Takhsh E., Blakemore A. I., Duff G. W. Single base polymorphism at -511 in the human interleukin-1 beta gene (IL1 beta). Hum Mol Genet. 1992 Sep;1(6):450–450. doi: 10.1093/hmg/1.6.450. [DOI] [PubMed] [Google Scholar]

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