TELOMERE SHORTENING IN THE COLONIC MUCOSA OF PATIENTS WITH ULCERATIVE-COLITIS

Telomere length in human somatic cells gradually decreases with the nu mber of cell divisions and is regarded as a marker of somatic cell tur nover. Mucosal cells of the affected colon show rapid turnover in indi viduals with active ulcerative colitis (UC), Telomere length was deter mined by Southern blot analysis of terminal restriction fragments (TRF s) from the colonic mucosa of 17 patients with UC in remission, two of whom showed dysplasia, and 17 control subjects without colitis. For e ach individual, mean TRF length was compared between rectal mucosa and unaffected cecal mucosa. The mean TRF length of the rectal mucosa was significantly less than that of cecal mucosa in UC patients (7.87 +/- 0.36kb versus 8.77 +/- 0.21kb P = 0.0015, Wilcoxon signed rank test), whereas no significant difference was detected in the control subject s. The extent of telomere shortening was 10.6 +/-: 3.35% in UC patient s, compared with 0.8 +/- 0.64% in noncolitis controls (P = 0.0024, Man n-Whitney U-test). Four UC patients, two of whom had dysplasia, showed telomere shortening of more than 20% in the rectal mucosa. These obse rvations suggest that telomere shortening in the colonic mucosa of ind ividuals with UC may represent the history of mucosal inflammation dur ing disease of long duration, and that it may contribute to aneuploidy in UC.