Table 2.
Summary of potential targets for drug repurposing in SSc based on promoter capture Hi‐C data
| Genome‐wide association study locus | Promoter capture Hi‐C interacting genes | Cell type with interactions | Genes in strong protein–protein interaction | Targeted drug | Disease indication* |
|---|---|---|---|---|---|
| rs2056626 | CREG1 | CD4+ T cells | TUBB4B | Colchicine | Osteoarthritis, advanced fibrosis |
| rs4076852 | RPP14 | CD4+ T cells, CD14+ monocytes | KEAP1 | Dimethyl fumarate | Psoriasis, multiple sclerosis, disseminated sclerosis |
| AGTR1 | Candesartan | Type 1 diabetes mellitus | |||
| HSPA8 | Forigerimon | Systemic lupus erythematosus | |||
| rs230534 | NFKB1 | CD4+ T cells | IL12B | Ustekinumab | Psoriasis, Crohn's disease, ulcerative colitis |
| IL1R1 | Anakinra | Rheumatoid arthritis | |||
| IL23A | Tildrakizumab | Psoriasis | |||
| JAK2 | Tofacitinib | SSc, rheumatoid arthritis, ulcerative colitis, interstitial lung disease, Takayasu arteritis | |||
| NR3C1 | Methylprednisolone† | Rheumatoid arthritis, Crohn's disease, psoriatic arthritis, ulcerative colitis, Behçet's syndrome | |||
| UBE2D3 | CD4+ T cells, CD14+ monocytes | KEAP1 | Dimethyl fumarate | Psoriasis, multiple sclerosis, disseminated sclerosis | |
| rs685985 | SDCBP | CD4+ T cells | IMPDH1 | Mycophenolic acid† | Systemic lupus erythematosus, immunosuppression |
| TUBB4B | Colchicine | Osteoarthritis, advanced fibrosis | |||
| CHD7 | CD4+ T cells | PPARG | Mesalamine | Crohn's disease, ulcerative colitis | |
| rs11217020 | CXCR5 | CD4+ T cells, CD14+ monocytes | S1PR3 | Fingolimod | Multiple sclerosis, disseminated sclerosis |
| rs1378942 | CSK | CD4+ T cells, CD14+ monocytes | FLT4 | Nintedanib | SSc, idiopathic pulmonary fibrosis, interstitial lung disease |
| COX5A | CD4+ T cells, CD14+ monocytes | NDUFB10 | Metformin | Type 1 diabetes mellitus, type 2 diabetes mellitus | |
| rs883770 | IKZF3 | CD4+ T cells | JAK1 | Baricitinib | Rheumatoid arthritis |
| JAK3 | Upadacitinib | Rheumatoid arthritis | |||
| IL2RA | Basiliximab | Type 1 diabetes mellitus | |||
| ERBB2 | CD4+ T cells, CD14+ monocytes | IL6R | Tocilizumab | SSc, rheumatoid arthritis, juvenile idiopathic arthritis, giant cell arteritis | |
| JAK kinases | Tofacitinib | SSc, rheumatoid arthritis, ulcerative colitis, interstitial lung disease, Takayasu arteritis | |||
| rs2305743 | PIK3R2 | CD4+ T cells | ADRA1B | Epinephrine | Crohn's disease |
| AGTR1 | Candesartan | Type 1 diabetes mellitus | |||
| EDNRA | Bosentan | SSc, idiopathic pulmonary fibrosis, pulmonary arteria hypertension | |||
| JAK1 | Baricitinib | Rheumatoid arthritis | |||
| JAK kinases | Tofacitinib | SSc, rheumatoid arthritis, ulcerative colitis, interstitial lung disease, Takayasu arteritis | |||
| PDGFRB | Nintedanib | SSc, idiopathic pulmonary fibrosis, interstitial lung disease | |||
| RAB3A | CD4+ T cells, CD14+ monocytes | HSPA8 | Forigerimod | Systemic lupus erythematosus |
*
Only related immune‐mediated diseases listed. All clinical trials for use in these diseases at least completed phase III.
†
Drugs currently in phase III or earlier phase clinical trials in systemic sclerosis (SSc).