Skip to main content
PMC home page
Gut logoLink to Gut
. 1997 May;40(5):623–627. doi: 10.1136/gut.40.5.623

Lack of association between an interleukin-1 receptor antagonist gene polymorphism and ulcerative colitis.

U T Hacker 1, M Gomolka 1, E Keller 1, A Eigler 1, C Folwaczny 1, H Fricke 1, E Albert 1, K Loeschke 1, S Endres 1
PMCID: PMC1027165  PMID: 9203941

Abstract

BACKGROUND: Recently, the association of a polymorphism in the gene coding for the anti-inflammatory cytokine interleukin-1 receptor antagonist with ulcerative colitis has been reported. This was interpreted as a possible genetic predisposition for severity of the inflammatory response. AIMS: To examine this polymorphism in a southern German population. SUBJECTS: The study included 234 healthy controls, 57 patients with ulcerative colitis, including 31 patients with pancolitis, 44 first degree healthy relatives of patients with ulcerative colitis, and 65 patients with Crohn's disease. METHODS: Genotypes were determined by a polymerase chain reaction amplification of the intron 2 fragment harbouring a variable number of tandem repeat nucleotide sequences. Amplification products were separated on a 2% agarose gel. RESULTS: The allele frequency for allele 2 was 27% in healthy controls, 28% in Crohn's disease, and 21% in patients with ulcerative colitis. The same allele frequency (21%) was found in a subgroup of patients with ulcerative colitis affecting the whole colon. Thus for allele 2 as well as for all other alleles, genotypes, or carriage rates no significant differences were found compared with controls. All allele frequencies in the control population were similar to those in earlier studies. CONCLUSIONS: No association of a polymorphism in the interleukin-1 receptor antagonist gene with ulcerative colitis could be identified in this southern German population. The findings of an earlier study reporting an increased frequency of allele 2, particularly in patients with pancolitis, could not be confirmed.

Full text

PDF
623

Images in this article

624Image
on p.624

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arend W. P. Interleukin 1 receptor antagonist. A new member of the interleukin 1 family. J Clin Invest. 1991 Nov;88(5):1445–1451. doi: 10.1172/JCI115453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carter D. B., Deibel M. R., Jr, Dunn C. J., Tomich C. S., Laborde A. L., Slightom J. L., Berger A. E., Bienkowski M. J., Sun F. F., McEwan R. N. Purification, cloning, expression and biological characterization of an interleukin-1 receptor antagonist protein. Nature. 1990 Apr 12;344(6267):633–638. doi: 10.1038/344633a0. [DOI] [PubMed] [Google Scholar]
  3. Casini-Raggi V., Kam L., Chong Y. J., Fiocchi C., Pizarro T. T., Cominelli F. Mucosal imbalance of IL-1 and IL-1 receptor antagonist in inflammatory bowel disease. A novel mechanism of chronic intestinal inflammation. J Immunol. 1995 Mar 1;154(5):2434–2440. [PubMed] [Google Scholar]
  4. Cominelli F., Nast C. C., Duchini A., Lee M. Recombinant interleukin-1 receptor antagonist blocks the proinflammatory activity of endogenous interleukin-1 in rabbit immune colitis. Gastroenterology. 1992 Jul;103(1):65–71. doi: 10.1016/0016-5085(92)91096-m. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Dinarello C. A. Biologic basis for interleukin-1 in disease. Blood. 1996 Mar 15;87(6):2095–2147. [PubMed] [Google Scholar]
  7. Dinarello C. A. The interleukin-1 family: 10 years of discovery. FASEB J. 1994 Dec;8(15):1314–1325. [PubMed] [Google Scholar]
  8. Dinarello C. A., Thompson R. C. Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. Immunol Today. 1991 Nov;12(11):404–410. doi: 10.1016/0167-5699(91)90142-G. [DOI] [PubMed] [Google Scholar]
  9. Eisenberg S. P., Brewer M. T., Verderber E., Heimdal P., Brandhuber B. J., Thompson R. C. Interleukin 1 receptor antagonist is a member of the interleukin 1 gene family: evolution of a cytokine control mechanism. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5232–5236. doi: 10.1073/pnas.88.12.5232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eisenberg S. P., Evans R. J., Arend W. P., Verderber E., Brewer M. T., Hannum C. H., Thompson R. C. Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist. Nature. 1990 Jan 25;343(6256):341–346. doi: 10.1038/343341a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Farmer R. G., Michener W. M., Mortimer E. A. Studies of family history among patients with inflammatory bowel disease. Clin Gastroenterol. 1980 May;9(2):271–277. [PubMed] [Google Scholar]
  13. Ferretti M., Casini-Raggi V., Pizarro T. T., Eisenberg S. P., Nast C. C., Cominelli F. Neutralization of endogenous IL-1 receptor antagonist exacerbates and prolongs inflammation in rabbit immune colitis. J Clin Invest. 1994 Jul;94(1):449–453. doi: 10.1172/JCI117345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hannum C. H., Wilcox C. J., Arend W. P., Joslin F. G., Dripps D. J., Heimdal P. L., Armes L. G., Sommer A., Eisenberg S. P., Thompson R. C. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature. 1990 Jan 25;343(6256):336–340. doi: 10.1038/343336a0. [DOI] [PubMed] [Google Scholar]
  15. Hannum C. H., Wilcox C. J., Arend W. P., Joslin F. G., Dripps D. J., Heimdal P. L., Armes L. G., Sommer A., Eisenberg S. P., Thompson R. C. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature. 1990 Jan 25;343(6256):336–340. doi: 10.1038/343336a0. [DOI] [PubMed] [Google Scholar]
  16. Hyams J. S., Fitzgerald J. E., Wyzga N., Treem W. R., Justinich C. J., Kreutzer D. L. Characterization of circulating interleukin-1 receptor antagonist expression in children with inflammatory bowel disease. Dig Dis Sci. 1994 Sep;39(9):1893–1899. doi: 10.1007/BF02088122. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Nishiyama T., Mitsuyama K., Toyonaga A., Sasaki E., Tanikawa K. Colonic mucosal interleukin 1 receptor antagonist in inflammatory bowel disease. Digestion. 1994;55(6):368–373. doi: 10.1159/000201167. [DOI] [PubMed] [Google Scholar]
  22. Roth M. P., Petersen G. M., McElree C., Vadheim C. M., Panish J. F., Rotter J. I. Familial empiric risk estimates of inflammatory bowel disease in Ashkenazi Jews. Gastroenterology. 1989 Apr;96(4):1016–1020. doi: 10.1016/0016-5085(89)91618-1. [DOI] [PubMed] [Google Scholar]
  23. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Satsangi J., Welsh K. I., Bunce M., Julier C., Farrant J. M., Bell J. I., Jewell D. P. Contribution of genes of the major histocompatibility complex to susceptibility and disease phenotype in inflammatory bowel disease. Lancet. 1996 May 4;347(9010):1212–1217. doi: 10.1016/s0140-6736(96)90734-5. [DOI] [PubMed] [Google Scholar]
  26. Tarlow J. K., Blakemore A. I., Lennard A., Solari R., Hughes H. N., Steinkasserer A., Duff G. W. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum Genet. 1993 May;91(4):403–404. doi: 10.1007/BF00217368. [DOI] [PubMed] [Google Scholar]
  27. Thompson R. C., Dripps D. J., Eisenberg S. P. Interleukin-1 receptor antagonist (IL-1ra) as a probe and as a treatment for IL-1 mediated disease. Int J Immunopharmacol. 1992 Apr;14(3):475–480. doi: 10.1016/0192-0561(92)90178-n. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Tysk C., Lindberg E., Järnerot G., Flodérus-Myrhed B. Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut. 1988 Jul;29(7):990–996. doi: 10.1136/gut.29.7.990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yang H., McElree C., Roth M. P., Shanahan F., Targan S. R., Rotter J. I. Familial empirical risks for inflammatory bowel disease: differences between Jews and non-Jews. Gut. 1993 Apr;34(4):517–524. doi: 10.1136/gut.34.4.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yang H., Rotter J. I., Toyoda H., Landers C., Tyran D., McElree C. K., Targan S. R. Ulcerative colitis: a genetically heterogeneous disorder defined by genetic (HLA class II) and subclinical (antineutrophil cytoplasmic antibodies) markers. J Clin Invest. 1993 Aug;92(2):1080–1084. doi: 10.1172/JCI116613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Youngman K. R., Simon P. L., West G. A., Cominelli F., Rachmilewitz D., Klein J. S., Fiocchi C. Localization of intestinal interleukin 1 activity and protein and gene expression to lamina propria cells. Gastroenterology. 1993 Mar;104(3):749–758. doi: 10.1016/0016-5085(93)91010-f. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES