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

There is evidence of a disbalance in the inflammatory regulation of patient s with inflammatory bowel diseases (IBD). Interleukin-1 beta plays an impor tant role in the pro-inflammatory response. Our aim was to study the influe nce which IL1B gene polymorphisms may have on the severity and course of th ese 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 cha in 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 posit ion +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 w as significant in patients with non-perforating disease (P=0.002), but was not present in patients with perforating-fistulizing disease. The distribut ion of both allelic pairs in the non-fistulizing group proved to be signifi cantly 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. Amo ng carriers of allele 2 at position -511, UC patients with more severe blee ding symptoms (P=0.006) were less frequently found. These results suggest t hat IL1B gene polymorphisms participate in determining the course and sever ity of inflammatory bowel disease and contribute to explain the heterogenei ty of these diseases.