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P004. Transcriptome of unfolded protein response (UPR) genes in the colonic mucosa of patients with ulcerative colitis

G. Fonseca-Camarillo, A. Peredo-Escarcega, J. Yamamoto-Furusho, IBD Clinic, Instituto Nacional de Ciencias Medicas y Nutricion, Gastroenterology, Mexico, Mexico

Background

Inflammatory bowel disease (IBD) is a chronic intestinal disorder of unknown etiology. It has been postulated that IBD patients have a dysregulation of cellular responses such as autophagy. Another pathway that is closely involved with autophagy and mutually cross-regulated is the unfolded protein response (UPR), which is induced by endoplasmic reticulum (ER) stress. Genes involved in the UPR region are XBP1, ORMDL3, AGR2, and IRGM have also been genetically associated with ulcerative colitis (UC). The aim of the present study was to evaluate the transcriptome panel of UPR genes in the colonic mucosa from UC patients.

Methods

We studied a total of 60 patients with definitive diagnosis of UC (30 active and 30 in remission) and healthy control group (N = 30) without endoscopic and histological evidence of colonic inflammation. In all groups, the XBP1, ORMDL3, AGR2, and IRGM gene expression was measured by real time polymerase chain reaction (RT-PCR) in colonic biopsies as well as GAPDH as housekeeping gene. The statistical analysis was performed by SPSS 17 version. A P value <0.05 was considered as significant.

Results

Patients with UC in remission had significantly higher IRGM gene expression in colonic mucosa compared to active UC patients and healthy controls (P = 0.01 and P = 0.01 respectively). The medical treatment response was associated with high gene expression of IRGM (P = 0.001). Conversely, XBP1 and AGR2 gene expression were decreased in remission UC compared to active UC patients and controls (P = 0.04 and P = 0.04, respectively). The ORDML3 expression was decreased in patients with active UC compared to remission UC patients and healthy control group (P = 0.02 and P = 0.0001, respectively). The ORDML3 levels were decreased in UC remission compared to the healthy control group (P = 0.003).

Conclusion

The genes involved in the UPR region (XBP1, ORMDL3 and AGR2) showed an altered expression in the colonic mucosa from patients with UC, suggesting that these genes could be involved in the pathogenesis of UC.