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P137 The oxido-reductases enzymes (TDO2 and SOD2) in colonic mucosa are markers associated with histological activity and clinical course in ulcerative colitis

J. Yamamoto-Furusho*, L. Salazar-Salas, G. Fonseca-Camarillo

IBD Clinic, Instituto Nacional de Ciencias Medicas y Nutricion, Gastroenterology, Mexico City, Mexico

Background

Ulcerative colitis (UC) is a polygenic and multifactorial disease. The TDO2 gene encodes for an oxidoreductase enzyme participating in the pathway of tryptophan and having an immunosuppressive function. However, the SOD2 gene encodes an antioxidant enzyme (superoxide dismutase magnesium) located in the mitochondrial matrix that protects cells from oxidative stress by scavenging free radicals. No previous studies have evaluated the role of oxidoreductases enzymes (TDO2 and SOD2) expression in the colonic mucosa from patients with UC. The aim was to measure the gene expression of SOD2 and TDO2 in the colonic mucosa from patients with UC and to determine its association with clinical characteristics of the disease.

Methods

We evaluated a total of 40 patients with definitive diagnosis of UC and 20 normal controls without endoscopic and histologic evidence of colonic inflammation. Colonic mucosal biopsies were taken by colonoscopy and preserved in RNA later. The total ribonucleic acid (RNA) was extracted and cDNA was obtained by polymerase chain reaction (PCR). The TDO2 and SOD2 relative gene expression was measured by real-time PCR, using specific primers and GAPDH gene as a reference, was analysed for normalisation purposes and quality control. Statistical analysis was performed using SPSS version 20. A value of p <0.05 was considered as significant.

Results

We studied 40 patients with UC (20 active and 20 in remission, 50% female and 50% male (mean age at diagnosis of 40 years). The extent of disease 52.8% had pancolitis, 16.7% left colitis, and 30.6% proctosigmoiditis. In the clinical course, 66.7% had an intermittent activity, 30.6% initial activity and then long-term remission, and 2.8% continuous activity. The degree of UC activity was 16.7% severe, 27.8% moderate, 8.3% mild, and 47.2% were in remission. The TDO2 and SOD2 gene expression were significantly higher in patients with active UC compared with the normal control group without inflammation (p = 0.001 and p = 0.001, respectively) and UC in remission and controls (p = 0.04 and p = 0.001, respectively). The gene expression of SOD2 was associated with severe histological activity (OR = 26.4, 95% CI, 4.4–157.2, p = 0.00004). The over-expression of TDO2 was associated with clinical course characterised by the presence of initial activity and then prolonged remission more than 5 years (p = 0.06, OR = 4.7, 95% CI, 0.85 to 26).

Conclusion

The genes TDO2 and SOD2 were up regulated in the colonic mucosa from patients with active UC. The gen TDO2 was associated with benign clinical course of UC, and the gene expression of SOD2 was associated with histologial activity in the colonic mucosa of UC patients.