Statistics from Altmetric.com
- CARD, caspase activating recruitment domain
- MMP, matrix metalloproteinase
- PWM, pokeweed mitogen
- TDT, transmission disequilibrium test
Crohn’s disease (MIM 266600) and ulcerative colitis (MIM 191390) are the major forms of inflammatory bowel disease (MIM 601458), the prevalence of Crohn’s disease being more than 1/1000 in the Western countries.1 Inflammatory bowel disease is characterised by chronic relapsing intestinal inflammation, and its pathogenesis probably involves microbial, immunological, environmental, and genetic factors.2,3 Recent genetic association studies have shown that sequence variations in the Caspase Activating Recruitment Domain (CARD15) gene (MIM605956, formerly named NOD2) on chromosome 16q are a strong genetic factor for Crohn’s disease but not for ulcerative colitis.4–6CARD15 represents the first major Crohn’s disease susceptibility gene identified, and its identification might facilitate the uncovering of other genetic factors for the disease.
The matrix metalloproteinases (MMP) are a group of matrix degrading enzymes that play an important role in the pathogenesis of various inflammatory diseases including osteoarthritis, rheumatoid arthritis, atherosclerosis, cancers, and inflammatory bowel disease.7 We have shown that, of four MMPs studied (interstitial collagenase, gelatinase A and B, and stromelysin-1), stromelysin-1 in particular is directly involved in mucosal destruction following T cell activation in the human fetal gut.8 Furthermore, patients with Crohn’s disease have increased expression of stromelysin-1 in the mucosa at both the mRNA and protein levels.9 Microarray techniques have demonstrated that stromelysin-1 expression is increased 8.7-fold in the mucosa of patients with Crohn’s disease compared with healthy controls (Pender SLF, unpublished data), and have also shown that stromelysin-1 expression is 8.2-fold higher relative to controls in PWM stimulated human fetal gut explant culture.10 Thus, although the stromelysin-1 gene on chromosome 11q23 is not located within the particular chromosomal regions (19p13, 16q12, 16p, 14q11–q12, 12p13.2–q24.1, 6p, 5q31, and 1p36) that have been shown to be in linkage with inflammatory bowel disease (MIN 266600), it is a strong …
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.