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CAMIP causal chains
CAMIP stands for Causal Analysis of Mechanistic Inference in Pharmacogenomics. Each released row links a receptor-peak-associated pharmacogene to an inducer and relevant drug associations through a reviewed mechanistic chain. Drug context is informed by PharmGKB clinical annotations and the cited literature. These receptors govern the inducible enzymes and transporters that handle a large share of clinically used drugs and their interactions. The CYP3A subfamily alone metabolizes roughly 30% of marketed drugs, as summarized in a CYP450 metabolism review, and the panel further spans CYP2C9, CYP2C19, CYP1A2, CYP2C8, CYP2A6, UGT1A1 and major hepatic transporters, covering many first line agents prone to drug interactions driven by induction. CAMIP describes mechanism only and gives no dosing, monitoring, severity, or treatment recommendations.
AhR axis
Canonical inducer: Smoking; PAHs; Experimental TCDD
| Gene | Regulatory element | Predicted effect if AhR binding is reduced | Drug context | Review | Refs |
|---|---|---|---|---|---|
| ALDH3A1 | overlapping the TSS | Reduced AhR-mediated induction of ALDH3A1 would lower ALDH3A1-mediated oxidation of aldophosphamide; increased retention of the active intermediate may sensitise tumour cells to cyclophosphamide. | cyclophosphamide; doxorubicin; fluorouracil | Pharmacist reviewed | 24677340 |
| CYP1A1 | at promoter -276 bp | Diminished AhR-mediated transactivation of CYP1A1, reducing both basal and inducible CYP1A1 expression and thereby attenuating local bioactivation of procarcinogens such as benzo[a]pyrene. | deferasirox; carbamazepine; phenobarbital; phenytoin; valproic acid; capecitabine | Pharmacist reviewed | 31199573, 37707797 |
| CYP1A2 | at promoter -3123 bp | Reduced receptor-mediated transactivation of CYP1A2 diminishes the inducibility of this major hepatic CYP; substrate clearance is correspondingly less enhanced in the induced state, which may raise exposure to narrow-therapeutic substrates. | clozapine; caffeine; leflunomide; paroxetine; olanzapine; escitalopram | Pharmacist reviewed | 19961320, 37707797 |
FXR axis
Canonical inducer: Obeticholic acid; Experimental GW4064
| Gene | Regulatory element | Predicted effect if FXR binding is reduced | Drug context | Review | Refs |
|---|---|---|---|---|---|
| SLC10A1 | in distal enhancer +11900 bp | Reduced FXR binding would weaken FXR-driven SHP induction; with SHP-mediated repression relieved, SLC10A1/NTCP expression would rise, thus increasing the hepatic clearance of NTCP substrates. | rosuvastatin | Pharmacist reviewed | 23299969, 23930675 |
PXR axis
Canonical inducer: Rifampicin
| Gene | Regulatory element | Predicted effect if PXR binding is reduced | Drug context | Review | Refs |
|---|---|---|---|---|---|
| CYP3A4 | at promoter -137 bp | CYP3A subfamily enzymes metabolize ~30% of clinically used drugs. Blunted receptor-mediated induction of CYP3A4 reduces its inducible metabolic capacity under PXR inducers. | quetiapine; tacrolimus; fentanyl; cyclosporine; sufentanil; simvastatin | Pharmacist reviewed | 10570062, 23333322, 40301309 |
| UGT1A1 | at promoter -137 bp | Blunted receptor-mediated induction of UGT1A1, reducing the inducible glucuronidation capacity. For irinotecan, reduced glucuronidation of the active metabolite SN-38 may increase toxicity. | FOLFIRI; irinotecan; atazanavir; atazanavir / ritonavir; sacituzumab govitecan; SN-38 | Pharmacist reviewed | 25275310, 40301309, 26417955, 17728214 |
| CYP2C9 | at promoter -1557 bp | Blunted receptor-mediated induction of CYP2C9 reduces the inducible metabolism of narrow-therapeutic-index substrates such as warfarin and phenytoin. | warfarin; phenytoin; celecoxib; fluvastatin; ibuprofen; meloxicam | Pharmacist reviewed | 25275310, 40301309 |
| CYP2C8 | at promoter -1846 bp | Blunted receptor-mediated induction of CYP2C8 reduces the inducible metabolic clearance of substrates such as repaglinide and paclitaxel. | ibuprofen; tacrolimus; rosiglitazone; pioglitazone; amodiaquine; paclitaxel | Pharmacist reviewed | 15933212, 25275310 |
| CYP2C19 | in distal enhancer +14490 bp | Blunted receptor-mediated induction of CYP2C19 lowers antiplatelet effect of the prodrug clopidogrel, and raises exposure of voriconazole. | clopidogrel; voriconazole; omeprazole; lansoprazole; citalopram; escitalopram | Pharmacist reviewed | 12869636, 25275310, 40301309, 38899464, 27981572 |
| CYP2A6 | in distal enhancer +21719 bp | Blunted receptor-mediated induction of CYP2A6 decreases the hepatic oxidative metabolism and clearance of its substrates such as nicotine and coumarin. | nicotine; coumarin; tegafur; efavirenz; letrozole; metronidazole | Pharmacist reviewed | 16857725, 25275310 |
Drug context may represent a substrate, inhibitor, inducer, prodrug or other literature-supported association; it should not be interpreted as a uniform substrate classification. Causal chains describe mechanism only and are scientific predictions, not medical advice.