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P173. Peroxisome proliferator-activated receptors family is involved in the response to treatment and clinical course in patients with ulcerative colitis

J. Yamamoto-Furusho, M. Jacintez-Cazares, G. Fonseca-Camarillo, IBD Clinic, Instituto Nacional de Ciencias Medicas y Nutricion, Gastroenterology, Mexico, Mexico

Background

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of nuclear hormone receptor superfamily comprising three isotypes: PPAR-α, PPAR-γ, and PPAR-β/δ. They play an important role in the regulation of intestinal inflammation. The colon is a major organ that expresses PPAR-γ in epithelial cells. This is the first study, to our best knowledge, with a larger sample that correlates the PPARs family gene expression in the colonic mucosa from patients with UC and disease activity. The aim of the present study was to characterize the gene expression of PPAR's family in the colonic mucosa from patients with UC and normal controls.

Methods

We studied a total of 77 individual who were divided in two groups: (1) 46 patients with confirmed diagnosis of UC and (2) 31 normal controls. Colonic biopsies were taken from colonoscopy and total RNA was extracted and isolated using the high pure RNA tissue. Two hundred nanograms of RNA was reverse-transcribed into cDNA with random hexamer primers and the gene expression of PPAR-α, PPAR-γ, and PPAR-β/δ as well as the GAPDH as housekeeping gene for normalization purposes were measured by Real Time Polymerase Chain Reaction (RT-PCR). Statistical analysis was performed by using SPPS 18 version. A P value <0.05 was considered as significant.

Results

We studied a total of 77 individuals who were divided in two groups: 46 patients with UC (22 men and 24 women) and 31 normal controls (12 men and 19 women). The PPAR-α expression was significantly decreased in patients with active UC compared to remission UC group (P = 0.001) and normal controls (P = 0.0001). We found that low expression of PPAR-α gene confers a higher risk of UC activity (P = 0.0001, OR = 22.6). We observed an increased of PPAR-α expression in patients with UC who were treated with only 5-aminosalicylates compared to those who received any other combined therapy (P = 0.03, OR = 0.08). The PPAR-γ expression was decreased in the active UC group compared to UC in remission (P = 0.01) and normal control groups (P = 0.0001). An increased expression of PPAR-γ gene was associated with mild clinical course of disease (P = 0.0006, OR = 0.05). No expression of PPAR-β/δ was found in the colonic mucosa from UC patients and normal controls, it means that this gene is not expressed in the colon.

Conclusion

The gene expression of PPAR-α and PPAR-γ were decreased in patients with active UC compared to UC remission and normal control groups. Our results suggest that patients with high gene expression of PPARs have a better response to medical treatment and mild clinical course of disease.