Table 5 Summary of prioritized genes associating MetS with cancer or inflammation
Biological mechanism | Annotated genes | Biological function | Association identifier phenotype | Relevance to cancer and/or inflammation | Evidence |
|---|---|---|---|---|---|
Cell cell adhesion and cell motility | CDH18 | A member of Calcium-dependent cell adhesion molecules subfamily type 2 N-cadherin, affects morphogenesis, growth and tissue homeostasis. | weight, BMI, WC, HC and RQ | Formation, growth, invasion and migration of malignant tumors, including Crohn’s disease and prostate cancer. Ectopic expression in breast cancer cells promotes motility, invasion and metastasis. | SNP associations |
CDH12 | A member of the cadherin family. | leptin | Its homologue, CDH11, promotes synovial fibroblasts to secret pro-inflammatory cytokines. | SNP associations | |
CTNND2 | A partner molecule in the cadherin complex. It is a transcription activator. | BMED | Involvement in cancer as above | SNP associations | |
| Â | MYO10 | An associate of the cadherin-catenin complex | Leankg, LDLppd, adiponectin, IL-6 | Function unclear, presumably involved in cancer as above | SNP associations, SNP cis-effects on gene expression, expression/MetS phenotype correlations |
Signal transduction | AKAP6 | An anchor protein for the AMP-activated protein kinase, a regulator of glycogen, sugar and lipid metabolism. | HC, RQ and REE/Lean | It might be involved in any cancer biology that is mediated through p53 | SNP associations |
PRKD1 | A protein kinase that exerts its function by phosphorylating target proteins. | WHR, Fatpct, Leanpct, and TNF-alpha | It is involved in prostate cancer through E-cadherin phosphorylation | SNP associations | |
| Â | PPP2R3C | It encodes the regulatory component of the protein ser/thr metallo-phosphatase. May regulate MCM3AP, which is a phosphorylation-dependent DNA replication initiation enzyme. Its homologue also play a role in the activation-induced cell death of B-cells. | DI | It may presumably be involved in cancer biology that relates MCM3. These include brain and thyroid cancer. It may also be involved in inflammation through its hypothetical function in B cell apoptosis. | SNP associations |
Transcription | TAG | A novel tumor antigen gene that is immunogenic. | REE,FG, HOMA, HMED | Testis cancer, skin melanoma and myelogenous leukemia. | SNP associations |
NPAS3 | A transcription factor which regulates neurogenesis, glucose metabolism and the linkage of the two. | Fatkg, Leankg, SubQF, TAF, REE/weight, TG, TC, cal. LDL-c, pulse, IL-1β, IL-6 | It is a brain tumor suppressor and a marker for survival. | SNP associations, | |
| Â | Â | Â | Â | SNP cis-effects on gene expression | |
NKX2-8 | A homeobox transcription factor | Weight and height | Fetal liver and hepatocellular carcinoma and lung cancer | SNP associations | |
BRMS1L | A homologue to transcription factor BRMS1, which functions in a histone acetylase complex that repress target genes | LMEDn and LDLppd | Breast cancer progression and melanoma metastasis | SNP associations | |
NOVA1 | It is a neuron-specific tumor antigen that has RNA-binding activity and functions to ensure correct pre-mRNA splicing of target RNA | BMI, WC, FG, FI, SI, AIR, HMED and sBP | It is involved in the paraneoplastic motor disorder | SNP associations | |
| Â | EGLN3 | It is a hydroxylase for target transcription factor HIF and mediates apoptosis in neuronal cells under development | IGR and LDL-c | It is involved in hemangioblastoma, clear cell renal carcinoma and formation of pheochromocytoma | SNP associations |
Protein sorting | MARCH11 | An ubiquitin ligase that is implicated in protein sorting and transport from trans-Golgi network to multivascular body. | Fatkg, FI, SI and IL-1β | Might be involved in pro-inflammatory cardiomyopathy. | SNP associations |
| Â | FBXL7 | Another ubiquitin ligase specific for phosphorylated protein degradation. | WHR | Might be involved in pro-inflammation as above | SNP associations, SNP cis-effects on gene expression |