CYP2C9, SLCO1B1, SLCO1B3, and ABCB11 polymorphisms in patients with bosentan-induced liver toxicity.
Bosentan is an endothelin receptor antagonist used as a first-line treatment in pulmonary arterial hypertension (PAH). Its main adverse effect is a dose-dependent liver toxicity. CYP2C9*2 has recently been shown to be associated with hepatotoxicity in PAH patients. We conducted a nested case-control study to further explore the relationship between functional polymorphisms of gene products involved in bosentan pharmacokinetics (OATP1B1, OATP1B3, and CYP2C9) or hepatobiliary transporters affected by bosentan (ABCB11) and bosentan-induced liver toxicity.
1] INSERM UMR 1042-HP2, Univ. Grenoble-Alpes, Grenoble, France [2] Clinical Pharmacology Unit, INSERM CIC1406, Grenoble University Hospital, Grenoble, France.
M
M
Roustit
Laboratory of Pharmacology, Grenoble University Hospital, Grenoble, France.
X
X
Fonrose
1] Univ. Paris -Sud, AP-HP, Centre National de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie, Département Hospitalo Universitaire (DHU), Thorax Innovation (TORINO), Hôpital de Bicêtre, Le Kremlin Bicêtre, France [2] INSERM UMRS_999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
D
D
Montani
1] Univ. Paris -Sud, AP-HP, Centre National de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie, Département Hospitalo Universitaire (DHU), Thorax Innovation (TORINO), Hôpital de Bicêtre, Le Kremlin Bicêtre, France [2] INSERM UMRS_999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
B
B
Girerd
1] Clinical Pharmacology Unit, INSERM CIC1406, Grenoble University Hospital, Grenoble, France [2] Laboratory of Pharmacology, Grenoble University Hospital, Grenoble, France.
F
F
Stanke-Labesque
Clinical Pharmacology Unit, INSERM CIC1406, Grenoble University Hospital, Grenoble, France.
N
N
Gonnet
1] Univ. Paris -Sud, AP-HP, Centre National de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie, Département Hospitalo Universitaire (DHU), Thorax Innovation (TORINO), Hôpital de Bicêtre, Le Kremlin Bicêtre, France [2] INSERM UMRS_999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
M
M
Humbert
1] INSERM UMR 1042-HP2, Univ. Grenoble-Alpes, Grenoble, France [2] Clinical Pharmacology Unit, INSERM CIC1406, Grenoble University Hospital, Grenoble, France.
J-L
JL
Cracowski
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D065128:Endothelin Receptor Antagonists; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D013449:Sulfonamides / Q000009:adverse effects*
D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D001189:Aryl Hydrocarbon Hydroxylases