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Background Diagnostic markers for distinguishing between Crohn disease (CD) and ulcerative colitis (UC) remain elusive. We studied whether methylation marks across the promoters of the transforming growth factor beta 1 (TGFβ1) and interleukin-6 genes have diagnostic utility. Methods A case-control study was carried out. Cases were treatment-naïve, diagnosed before age 20, and recruited from 3 pediatric gastroenterology clinics across Canada. Control patients did not have inflammatory bowel disease and were recruited from orthopedic clinics within the same hospitals as the gastroenterology clinics. Patient DNA from peripheral blood was processed to identify methylation sites (CpG) across the promoter regions of the TGFβ1 and interleukin-6 genes. After initial nonparametric univariate analyses, multivariate logistic regression models were fit. Models with the best fit (Akaike information criteria) and strongest discriminatory capabilities (area under the curve [AUC]) were identified, and P values were adjusted for multiple comparisons using the false discovery rate method. Results A total of 67 CD, 31 UC, and 43 control patients were included. The age distribution of the 3 groups was similar. Most CD patients had ileocolonic disease (44.8%) and inflammatory disease (88.1%). Most UC patients had extensive (71%) and moderate disease (51.6%). Logistic regression analysis revealed the following: 14 TGFβ1 CpG sites discriminated between CD and control patients (AUC = 0.94), 9 TGFβ1 CpG sites discriminated between UC and control patients (AUC = 0.99), 3 TGFβ1 CpG sites discriminated between CD and UC (AUC = 0.81), and 6 TGFβ1 CpG sites distinguished colonic CD from UC (AUC = 0.91). Conclusions We found that CpG methylation in the promoter of the TGFβ1 gene has high discriminative power for identifying CD and UC and could serve as an important diagnostic marker.

Background: Although genome-wide association studies (GWAS) and subsequent meta-analyses have confirmed associations between the PTPN2 (protein tyrosine phosphatase, nonreceptor type 2) gene and Crohn's disease (CD), the potential causal variants remain unidentified. We aimed to dissect potential causal CD-associated PTPN2 variants, assess their functional significance, and relate PTPN2 protein expression with inflammation in CD. Methods: A 3-stage study was carried out. In stage 1, we genotyped tagging single nucleotide polymorphisms (tag-SNPs) in the PTPN2 gene in a sample of patients with CD (

Background: Genome-wide association studies (GWAS) in Crohn's disease (CD) have identified associations with single-nucleotide polymorphism (SNP) rs11175593 at chromosome 12q12. The MUC19 and LRRK2 genes reside close to the GWAS signal, but it is as yet unclear which of the 2 genes represent the CD susceptibility genes. Methods: We studied associations between nonsynonymous coding variants in the MUC19 (5) and LRRK2 (3) genes in a case-control sample comprising CD cases aged