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Background  Epithelial-to-mesenchymal transition (EMT) is a phenomenon that allows the conversion of adherent epithelial cells to a mesenchymal cell phenotype, which enhances migratory capacity and invasiveness. Recent studies have suggested that EMT contributes to the pathogenesis of ulcerative colitis (UC). We investigated the promoter DNA methylation status of EMT-related genes in the colonic mucosa in UC.    Methods  Colonic biopsies were obtained from the rectal inflammatory mucosa of 86 UC patients and the non-inflammatory proximal colonic mucosa of 10 paired patients. Bisulfite pyrosequencing was used to quantify the methylation of 5 candidate CpG island promoters ( NEUROG1 ,  CDX1 ,  miR-1247 ,  CDH1 , and  CDH13 ) and  LINE1 .    Results  Using an unsupervised hierarchical clustering analysis, inflamed rectal mucosa was well separated from mucosa that appeared normal. The  CDH1  and  CDH13  promoters were significantly associated with patient age ( p  = 0.04, 0.03, respectively). A similar trend was found between those genes and the duration of disease ( CDH1 :  p  = 0.07,  CDH13 :  p  = 0.0002, mean of both:  p <0.00001). Several positive associations were found between hypermethylation and severe clinical phenotypes ( CDX1  and  miR-1247  and a refractory phenotype:  p  = 0.04 and 0.006, respectively.  miR-1247  and  CDH1  hyper methylation and a more severe Mayo endoscopic subscore:  miR-1247 :  p  = 0.0008,  CDH1 :  p  = 0.03, mean of both:  p  = 0.003). When the severe clinical phenotype was defined as having any of five phenotypes (hospitalized more than twice, highest Mayo endoscopic subscore, steroid dependence, refractory, or a history of surgery)  miR-1247  hypermethylation was associated with the same phenotype ( p  = 0.008).    Conclusions  Our data suggest that variability in the methylation status of EMT-related genes is associated with more severe clinical phenotypes in UC.

plos one

DNA Methylation Status of Epithelial-Mesenchymal Transition (EMT) - Related Genes Is Associated with Severe Clinical Phenotypes in Ulcerative Colitis (UC)