Table 5.
Functional and Biologic Relevance of Significant Differential Methylated Positions and Differentially Variable Positions Associated Crohn's Disease Recurrence Following Surgery
| Probe | Symbol | Function/relevance in inflammatory bowel disease |
|---|---|---|
| Differentially methylated probes | ||
| cg09916234 | NSD2/ WHSC1 | Nuclear receptor binding SET domain protein 2. Wolf-Hirschhorn syndrome, a multisystem chromosomal disorder associated with a deletion on chromosome 4. Also the probe maps close to the transcription start site of microRNA-943 that has been shown to accelerate airway inflammation in asthma.19 |
| cg24864518 | ∗ | This probe maps to an intergenic region close to the TSS of RASGEF1b, a guanine nucleotide exchange factor for Rap2, a member of the family of Rap G-protein signallers.20 |
| cg06058618 | EFNA3 | Ephrine A3. Tyrosine kinase family of receptors. Ephrine-mediated repulsion of cells have a role in maintaining the integrity of the gut epithelial layer and may modulate T-cell activation.21 Have previously been implicated in Crohn’s disease22 and ulcerative colitis,23 and have been postulated as a potential therapeutic target in Crohn’s disease.24 Also extensively implicated in gastric and hepatocellular cancers. Target of miR-210-3p. |
| cg23939096 | ∗ | Maps to a noncoding area. |
| cg25981920 | ∗ | Maps to a noncoding area close to LY6L lymphocyte antigen6 family member. |
| Differentially variable probes | ||
| cg24696067 | MAD1L1 | Mitotic arrest deficient like 1 acts as a spindle assembly checkpoint between metaphase and anaphase. MAD1L1 was a key finding in our previous work that demonstrated IBD-specific correlation between DNA methylation and gene expression.10 A different probe mapping to MAD1L1 was differentially methylated in colonic intraepithelial cells in UC.25 Because of its role in regulating the cell cycle, MAD1L1 is also implicated in a variety of cancers. |
| cg02208776 | HSPE1 | Heat shock protein family E that acts a chaperonin. Implicated in colorectal cancer.26,27 |
| cg18068256 | KRT37 | Keratin 37, a type I keratin that dimerises with type II keratins to form hair and nails. |
| cg00475456 | ∗ | Maps to an intergenic region close to PLXNA2 a plexin related in axon/nervous system development. |
| cg20310608 | LOC284798 | Uncharacterized LOC284798/ENSG00000230725. |
IBD, inflammatory bowel disease; UC, ulcerative colitis.