We read with interest the article by Matsuzawa et al showing an association between the K469E allele of intercellular adhesion molecule (ICAM)-1 gene and inflammatory bowel disease (IBD) in a Japanese population (Gut 2003;52:75–8). The ICAM-1 gene lies on chromosome 19p13, previously implicated in determining susceptibility to IBD,1 and codifies for a surface glycoprotein that belongs to the immunoglobulin superfamily. ICAM-1 plays an important role in the trafficking and activation of leucocytes and is upregulated in the inflamed mucosa of IBD patients. Matsuzawa et al found that the allelic frequency of K469 was significantly higher in both Crohn’s disease (CD) and ulcerative colitis (UC) patients than controls (Gut 2003;52:75–8). These data are in contrast with the results of two previous studies from the USA2 and Germany3 which showed no significant difference in K469 allele frequency between IBD patients and healthy controls. The G241R polymorphism of the ICAM-1 gene was also investigated in these studies, and IBD patients were stratified by antineutrophil cytoplasmic antibody (ANCA) status. In particular, Yang et al found a significantly increased frequency of the G241R polymorphism both in ANCA negative UC and ANCA positive CD patients2 while Braun et al showed an association between R241 allele and UC, independently of ANCA status.3
We also searched for the K469E mutation in 42 consecutive Italian IBD patients (31 males, mean age 36 (14) years), 17 with CD and 25 with UC, and 227 ethnically matched controls. Our preliminary results (see table 1▶), although obtained in a limited number of patients, are in contrast with the findings of Matsuzawa et al (Gut 2003;52:75–8) and confirm those obtained in Caucasians patients.2,3 The possible explanation for such a discrepancy in results is the influence of the different geographic distribution of the genetic mutation. Japanese patients with IBD have a genetic background that differs from Western patients, as also demonstrated recently for the NOD2/CARD15 gene polymorphisms. Indeed, several studies have reported an association between CD and NOD2/CARD15 mutations in Caucasians4–6 but not in Japanese cohorts.7,8 These data indicate that there may be significant genetic heterogeneity between different ethnic and racial IBD populations and environmental factors may play a leading role in the pathogenesis of IBD. Thus gene-environment interactions represent a crucial event in the pathogenesis of IBD and they cannot be considered as distinct entities.
Table 1 .
Allelic frequencies of the E/K469 ICAM-1 polymorphism in Italian patients affected by IBD, and in controls
Controls (n=227) | IBD (n=42) |
UC (n=25) |
CD (n=17) |
|
---|---|---|---|---|
Allelic frequency (%) | ||||
E469 | 45 | 45 | 46 | 44 |
K469 | 55 | 55 | 54 | 56 |
IBD, inflammatory bowel disease; UC, ulcerative colitis; CD, Crohn’s disease; ICAM, intercellular adhesion molecule.
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