Analysis of ICAM-1 gene polymorphism in immunologic subsets of inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) consists of ulcerative colitis (UC) and Crohn's disease (CD) - two chronic idiopathic inflammatory diseases of the gastrointestinal tract. Although exogenous or infectious agents might contribute to the pathogenesis or trigger the onset of disease, and the immune system certainly mediates tissue damage, it is clear from available data that the genetic factors determine the susceptibility of a given individual. IBD is characterized by a failure to downregulate the usual self-limited gut inflammatory response, suggesting that one or more of the predisposing genes could be those that determine the level of the immune response along the inflammatory pathway. Thus, we examined potential associations of intercellular adhesion molecule- 1 (ICAM- 1) gene polymorphisms with IBD or subsets of IBD by studying 118 UC and 130 CD patients, and 77 ethnically matched controls. These subjects were tested for antineutrophil cytoplasmic antibody (ANCA) and genotyped by PCR and ASO techniques for ICAM1 polymorphisms at codon 241 (exon 4) and codon 469 (exon 6). There was no significant difference between all UC patients, CD patients, and controls in either polymorphism. However, when stratified by ANCA status, ANCA-negative UC exhibited a borderline statistically significant increase of the R241 allele compared to ANCA-positive UC patients (28 vs. 12%, p = 0.05). In contrast, it was ANCA-positive CD that had a significantly increased allele frequency compared to ANCA-negative CD (36 vs. 16%, p = 0.018). Since the codon 241 polymorphism is in a functionally important domain III of ICAM-1, we may have identified an actual responsible genetic variation for genetically heterogeneous subsets of both of UC and of CD. Further characterization of ANCA and the understanding of functional significance of the ICAM-1 polymorphism will help delineate immunopathogenesis in certain subgroups of IBD patients.