Table 3.
Polymorphisms associated with responsiveness among patients with Crohn’s disease, ulcerative colitis, or inflammatory bowel disease treated with infliximab and adalimumab.
| rs | Genotype | Disease | Rf or NRf: n [p (OR/HR; 95% CI)] | Long/Short Term | Response Criteria | Gene | Pathway | Reference |
|---|---|---|---|---|---|---|---|---|
| rs2097432 | CC or CT | CD | NR: 1240 [4.24 × 10−13 (HR: 1.70; 1.48–1.94)]/NR: 178 (independent cohort) [8.80 × 10−4 (HR: 1.69; 1.26–2.28)] | ND | Persistence | HLA-DQA1*05 | Central role in the immune system by presenting peptides derived from extracellular proteins | [44] |
| rs116724455 | CC | CD and UC | NR: 474 [4.79 × 10−8 (OR: 19.90; 4.57–86.70)] | ND | Continued use at the time of study enrolment without failure | TNFSF4/18 | TNF-α pathway; inflammation | [45] |
| rs2228416 | TT | CD and UC | NR: 474 [5.24 × 10−6 (OR: 5.25; 2.33–11.8)] | ND | Continued use at the time of study enrolment without failure | PLIN2 | Lipid globule surface membrane material (development and maintenance of adipose tissue) | [45] |
| TNF-α 308 | G Allele | CD | R: 667 [8.6 × 10−5 (OR: 2.01; 1.42–2.84)] | ND | CD: CDAI, HBI | TNF-α | TNF-α pathway; inflammation | [43] |
| rs6100556 | TT | UC | NR: 340 [0.007; aHR: 2.95 (1.34–6.49)] | Long | Inmunogenic, pharmacokinetic, and pharmacodynamic criteria | PHACTR3 | Cell proliferation | [40] |
| rs3804099 | CC or CT | CD and UC | R: 738 [0.01 (ORadj: 1.80; 1.15–2.81)] | ND | Simple 3-step scale | TLR2 | Pathogen recognition | [36] |
| TNF-α -857 | C Allele | CD | R: 274 [0.013 (OR: 1.78; 1.13–2.80)] | ND | CD: Clinical outcome | TNF-α | TNF-α pathway; inflammation | [43] |
| TNF-α 238 | G Allele | CD | R: 274 [0.016 (OR: 2.20; 1.16–4.15)] | ND | CD: HBI | TNF-α | TNF-α pathway; inflammation | [43] |
| rs2097432 | CC o CT | CD | NR: 340 [0.019 (HR: 1.77; 1.10–2.85)] | Long | Clinical, biochemical, and endoscopic data or the need for abdominal surgery | HLA-DQA1*05 | Central role in the immune system by presenting peptides derived from extracellular proteins | [46] |
| rs2430561 | AA or AT | CD | R: 482 [0.02 (ORadj: 1.97; 1.13–3.42)] | ND | Simple 3-step scale | IFNG | Proinflammatory cytokine | [36] |
| rs4612666 | CT or TT | CD and UC | NR: 1783 [0.02 (OR: 0.73; 0.57–0.95)] | ND | Simple 3-step scale | NLRP3 | Regulation of inflammation, the immune response, and apoptosis | [4] |
| rs2241880 | AA | CD and UC | NR: 340 [0.02 (aHR: 0.51; 0.29–0.90)] | Long | Inmunogenic, pharmacokinetic, and pharmacodynamic criteria | ATG16L1 | Autophagy | [40] |
| rs11938228 | AA or AC | UC | NR: 256 [0.02 (OR: 0.55; 0.33–0.92)] | ND | Simple 3-step scale | TLR2 | Pathogen recognition | [4] |
| rs2188962 | CT or TT | UC | NR: 340 [0.029 (3.24; aHR: 1.13–9.35)] | Long | Inmunogenic, pharmacokinetic, and pharmacodynamic criteria | IRF1-AS1 | lncRNA | [40] |
| rs12343867 | TT or TC | CD | R: 1069 [0.03 (OR: 1.35; 1.02–1.78)] | ND | Simple 3-step scale | JAK2 | Proinflammatory cytokine | [4] |
| rs1554973 | CC or CT | CD and UC | NR: 1783 [0.03 (OR: 0.80; 0.65–0.98)] | ND | Simple 3-step scale | TLR4 | Pathogen recognition | [4] |
| rs6927172 | GG or CG | UC | NR: 256 [0.03 (ORadj: 0.34; 0.13–0.90)] | ND | Simple 3-step scale | TNFAIP3 | TNF-α pathway; inflammation | [36] |
| rs2395185 | GG | CD and UC | NR: 340 [0.039 (HR: 0.60; 0.37–0.98)] | Long | Clinical, biochemical, and endoscopic data or the need for abdominal surgery |
HLA-DQA1*05 | It plays a central role in the immune system by presenting peptides derived from extracellular proteins | [46] |
| rs4149570 | AA | CD | R: 1069 [0.04 (OR: 1.92; 1.02–3.60)] | ND | simple 3-step scale | TNFRSF1A | TNF-α pathway; inflammation | [4] |
| rs4848306 | AA or AG | UC | R: 256 [0.04 (ORadj: 2.69; 1.04–6.94)] | ND | Simple 3-step scale | IL1B | Proinflammatory cytokine | [36] |
| rs4645983 | TT | CD | R: 287 [0.04 (OR: 1.50; 1.34–1.68)] | ND | CDAI | CASP9 | Apoptosis | [47] |
| rs352139 | TT | CD | NR: 482 [0.04 (ORadj: 0.38; 0.16–0.94)] | ND | Simple 3-step scale | TLR9 | Pathogen recognition | [36] |
| rs4696480 | TT | UC | NR: 256 [0.04 (ORunadj: 0.47; 0.23–0.95)] | ND | Simple 3-step scale | TLR2 | Pathogen recognition | [36] |
| rs5030728 | AA | CD and UC | R: 1783 [0.04 (OR: 1.46; 1.01–2.11)] | ND | Simple 3-step scale | TLR4 | Pathogen recognition | [4] |
| rs2569190 | AA or AG | UC | NR: 256 [0.04 (ORunadj: 0.54; 0.30–0.98)] | ND | Simple 3-step scale | CD14 | Pathogen recognition | [36] |
| rs696 | GA or AA | CD and UC | R: 1783 [0.04 (OR: 1.25; 1.01–1.54)] | ND | Simple 3-step scale | NFKBIA | Pathogen recognition | [4] |
| rs1946518 | GT or TT | CD and UC | R: 1783 [0.04 (OR: 1.24; 1.01–1.53)] | ND | Simple 3-step scale | IL-18 | Proinflammatory cytokine | [4] |
| rs4251961 | CC or CT | UC | NR: 256 [0.04 (ORadj: 0.42; 0.18–0.98)] | ND | Simple 3-step scale | IL1RN | Proinflammatory cytokine | [36] |
| rs6098425 | CC | CD | NR: 340 [0.044 (aHR: 2.23; 1.02–4.88)] | Long | Inmunogenic, pharmacokineti, and pharmacodynamic criteria | CDKAL1 | Unknown | [40] |
| rs187238 | GG or GC | CD | R: 1069 [0.047 (OR: 1.35; 1.00–1.82)] | ND | Simple 3-step scale | IL-18 | Proinflammatory cytokine | [4] |
| rs4251961 | TC or CC | CD and UC | NR: 1783 [0.049 (OR: 0.81; 0.66–1.00)] | ND | Simple 3-step scale | IL1RN | Proinflammatory cytokine | [4] |
| rs10508884 | CC or CT | CD and UC | NR: 340 [0.049 (HR: 0.27; 0.07–1.11)] | Long | Inmunogenic, pharmacokineti, and pharmacodynamic criteria | CXCL12 | Proinflammatory cytokine | [40] |
| rs1800872 | CC | CD | NR: 209 [<0.05 (HR: 4.75; 1.16–19.52)] | Long | CD: wPCDAI; UC: PUCAI | IL-10 | Anti-inflammatory cytokine | [48] |
| rs2275913 | AA | CD | NR: 209 [<0.05 (HR: 0.32; 0.11–0.92)] | Long | CD: wPCDAI; UC: PUCAI | IL-17A | Proinflammatory cytokine | [48] |
| rs11465996 | CC or CG | UC | R: 309 [<0.05 (HR: 10.22; 1.85–56.50)] | Long | Simple 3-step scale | LY96 | Pathogen recognition | [36] |
| rs2275913 | AA or AG | UC | NR: 256 [0.05 (ORadj: 0.42; 0.18–1.00)] | ND | Simple 3-step scale | IL17A | Proinflammatory cytokine | [36] |
| rs10499563 | TT | CD | NR: 209 [0.05 (HR: 0.21; 0.05–0.95)] | Long | CD: wPCDAI; UC: PUCAI | IL-6 | Proinflammatory cytokine | [48] |
| rs6100556 | TT | CD and UC | NR: 340 [aHR: 0.025 (1.93; 1.09–3.42)] | Long | Inmunogenic, pharmacokinetic, and pharmacodynamic criteria | PHACTR3 | Cell proliferation | [40] |
NRf (allele/genotype frequency higher in nonresponsive patients), Rf (allele/genotype frequency higher in responsive patients), ND (not defined), UC (ulcerative colitis), CD (Crohn’s disease), wPCDAI (Weighted Pediatric Crohn’s Disease Activity Index), PUCAI (Pediatric Ulcerative Colitis Activity Index). R (response), NR (non-response), HR (hazards ratio), OR (odds ratio), CI (confidence interval).