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Microsatellite instability in non-neoplastic mucosa of patients with ulcerative colitis: effect of folate
M L Cravo1, C M Albuquerque, L Salazar de Sousa
1Serviço de Gastroenterologia, Centro de Investigação de Patobiologia Molecular, Instituto Portguês de Oncologia Francisco Gentil de Lisboa, Portugal.
Objective:
Microsatellite instability (MSI) detected in non-neoplastic mucosa of patients with ulcerative colitis has been ascribed to an excess of DNA damage associated with chronic inflammation. Folate deficiency, commonly found in patients with long-standing disease, could further contribute to this defect because folate is essential for DNA replication and repair. We evaluated MSI in the colonic mucosa of 26 patients with ulcerative colitis for >10 yr and 10 patients with Crohn's colitis and correlated MSI with folate status.
Methods:
DNA was amplified using primers directed at nine different loci. Folate concentrations in serum, whole blood, and colonic mucosa were determined using the Lactobacillus casei assay.
Results:
MSI was found in 3/23 patients (13%) with ulcerative colitis and in none of the patients with Crohn's colitis. All three patients with MSI had inactive histological disease, whereas all patients with active disease were negative for MSI (p = 0.08). Serum, whole blood, and colonic concentrations of folate were 30-50% lower in patients with MSI (p > 0.05), and folate supplements had been administered less frequently during the past 5-yr (p = 0.06). One of the patients with MSI was randomized to receive folate 5 mg/d for 6 months, and a clear change in MSI pattern was observed in three of six markers.
Conclusions:
A defect in DNA repair associated with a low folate status may be one additional cause for patients with ulcerative colitis exhibiting MSI in non-neoplastic mucosa.
Insights
Microsatellite instability (MSI) in ulcerative colitis patients may stem from folate deficiency impacting DNA repair. Lower folate levels were observed in patients with MSI, suggesting a potential link.
Area of Science:
- Gastroenterology
- Molecular Biology
- Nutritional Science
Background:
- Microsatellite instability (MSI) in non-neoplastic mucosa of ulcerative colitis (UC) patients is linked to DNA damage from chronic inflammation.
- Folate deficiency, common in long-standing UC, is crucial for DNA replication and repair, potentially exacerbating MSI.
Purpose of the Study:
- To evaluate MSI in the colonic mucosa of patients with ulcerative colitis (UC) and Crohn's colitis.
- To correlate MSI status with folate levels in these patients.
Main Methods:
- DNA amplification using primers for nine loci.
- Determination of folate concentrations in serum, whole blood, and colonic mucosa via Lactobacillus casei assay.
Main Results:
- MSI detected in 13% of UC patients, none in Crohn's colitis patients.
- Patients with MSI had lower serum, blood, and mucosal folate levels (30-50% reduction).
- Folate supplementation was less frequent in patients with MSI; one patient showed altered MSI patterns after folate therapy.
Conclusions:
- A DNA repair defect linked to low folate status may contribute to MSI in the non-neoplastic mucosa of UC patients.
- This finding suggests folate status is an important factor to consider in UC patients with MSI.