ORIGINAL PAPER

Immunogenetics

, Volume 49, Issue 6, pp 527-531

First online:

IL1B gene polymorphisms influence the course and severity of inflammatory bowel disease

  • A. NemetzAffiliated with2nd Department of Internal Medicine, Semmelweis University of Medical Sciences, Budapest, 1088, Szentkirályi u. 46. Hungary
  • , M. Pilar Nosti-EscanillaAffiliated withLaboratory Gastrointestinal Immunogenetics, Free University Faculty of Medicine, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands, E-mail: as.pena.humgen@med.vu.nl, Tel: +31-20 4448416, Fax: +31-20 4448418
  • , Tamás MolnárAffiliated with1st Department of Medicine, Albert Szent-Györgyi University, Szeged, 6720, Korányi fasor 8, Hungary
  • , Adorján KöpeAffiliated with2nd Department of Internal Medicine, Semmelweis University of Medical Sciences, Budapest, 1088, Szentkirályi u. 46. Hungary
  • , Ágota KovácsAffiliated withErzsébet Hospital, Budapest, 1074, Alsóerdõsor u.7. Hungary
  • , János FehérAffiliated with2nd Department of Internal Medicine, Semmelweis University of Medical Sciences, Budapest, 1088, Szentkirályi u. 46. Hungary
  • , Zsolt TulassayAffiliated with2nd Department of Internal Medicine, Semmelweis University of Medical Sciences, Budapest, 1088, Szentkirályi u. 46. Hungary
  • , Ferenc NagyAffiliated with1st Department of Medicine, Albert Szent-Györgyi University, Szeged, 6720, Korányi fasor 8, Hungary
  • , M. Asunción García-GonzálezAffiliated withLaboratory Gastrointestinal Immunogenetics, Free University Faculty of Medicine, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands, E-mail: as.pena.humgen@med.vu.nl, Tel: +31-20 4448416, Fax: +31-20 4448418
    • , A. S. PeñaAffiliated withLaboratory Gastrointestinal Immunogenetics, Free University Faculty of Medicine, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands, E-mail: as.pena.humgen@med.vu.nl, Tel: +31-20 4448416, Fax: +31-20 4448418

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Abstract

 There is evidence of a disbalance in the inflammatory regulation of patients with inflammatory bowel diseases (IBD). Interleukin-1β plays an important role in the pro-inflammatory response. Our aim was to study the influence which IL1B gene polymorphisms may have on the severity and course of these diseases. Ninety-six patients with ulcerative colitis (UC), 98 patients with Crohn's disease (CD), and 132 ethnically matched healthy individuals (HC) were typed for the polymorphic sites in the promoter region (position –511) and in exon 5 (position +3953) of the IL1B gene, using polymerase chain reaction (PCR)-based methods. In the CD group a significant association (P=0.009) was found in this pair of genes. Homozygotes for allele 1 at position +3953 were more often present (69% vs 31%) in the subgroup of patients carrying at least one copy of allele 2 at position –511. This association was significant in patients with non-perforating disease (P=0.002), but was not present in patients with perforating-fistulizing disease. The distribution of both allelic pairs in the non-fistulizing group proved to be significantly different from HC (P<0.05), UC (P<0.03), and the fistulizing group (P<0.05). There was a similar association in non-operated patients (P=0.024), whereas no such association was found in surgically treated patients. Among carriers of allele 2 at position –511, UC patients with more severe bleeding symptoms (P=0.006) were less frequently found. These results suggest that IL1B gene polymorphisms participate in determining the course and severity of inflammatory bowel disease and contribute to explain the heterogeneity of these diseases.

Key words Inflammatory bowel disease IL1B gene polymorphism Crohn's disease Ulcerative colitis Disease susceptibility