Table 11.
Functional and Biologic Relevance of Smoking-Related Probes Associated With CD
| Probe | Symbol | Function/relevance in IBD |
|---|---|---|
| CD-specific smoking-associated methylation probes | ||
| cg24497361 | RHOG | Ras homologue family member G. Rho family of small GTPases. Facilitates translocation of a GEF from the cytoplasm to the membrane. Found to be a smoking-related methylation probe by Dugue et al.30 |
| cg17777683 | CFLAR (cFLIP) | Caspase 8 and FADD-like apoptosis regulator. Regulator of apoptosis. Cigarette smoke decreases bronchial expression and increases susceptibility for cell death and DAMP release.31 Found to be smoking-related by Sikdar et al.32 |
| cg03088955 Table 10 - Top 20 Smoking associated methylation probes. |
JOSD1 | Josephin containing domain 1. Deubiquitinization enzyme. Involved in autophagy.33 |
| cg01218206 | SIK2 | Salt-induced kinase 2. Enable ATP binding activity. Involved in positive regulation of TORC1 and 2 signaling. Involved in TGF-β mediated apoptosis.34 Found to be a smoking-related methylation probe by Dugue et al.30 |
| cg05895711 | Found to be a smoking-related methylation probe by Dugue et al.30 | |
| cg08006672 | Seen by Sikdar et al32 in a meta-analysis of smoking-related probes to associate with smoking. | |
| cg09273683 | PIP4KA2 | Phosphatidylinositol-5,4-biphosphate 4 kinase type alpha 2. Kinase involved in secretion, cell proliferation, differentiation, and motility. Linked with schizophrenia and acute myeloid leukemia. A SNP in this region was found to be an environmental interactor between smoking and colorectal cancer.35 |
| cg18688062 | PSORS1C3 | Psoriasis Susceptibility 1 Candidate 3. Found to be a smoking-related methylation probe by Dugue et al.30 |
| cg21963318 | COX4I1 | Cytochrome c oxidase, a mitochondrial enzyme involved in mitochondrial respiration. |
| Smoking-related probe that intersects with CD vs control DMPs (smoking included as a covariate) | ||
| cg14753356 | Found to be smoking related by Sikdar et al32 and Dugue et al.30 | |
| cg00295485 | UXS1 | Found to be smoking related by Sikdar32 |
| cg21963318 | COX4I1 | Cytochrome c oxidase, as above |
| Smoking-related probe that intersects with CD vs control DMPs (smoking not a covariate) | ||
| cg13033858 | SSH1 | Slingshot protein phosphatase 1. Associated with colorectal cancer progression and prognosis.36 Found to be smoking related by Sikdar et al.32 |
NOTE. Yellow denotes probes not associated with smoking in previous meta-analyses of smoking and methylation (Gao, Sikar, Dugue et al).
CD, Crohn’s disease; DAMP, damage associated mucosal patterns; DMP, differentially methylated position; GEF, guanine nucleotide exchange factor; IBD, inflammatory bowel disease; SNP, single-nucleotide polymorphism.