Two patients with COMT inhibitor-induced hepatic dysfunction and UGT1A9 genetic polymorphism.
The authors report two cases of catechol-O-methyltransferase (COMT) inhibitor-induced asymptomatic hepatic dysfunction in women with Parkinson disease. The patients were genotyped for the UDP-glucuronosyltransferase (UGT) 1A9 gene (which encodes the main COMT inhibitor-metabolizing enzyme), and found to carry mutations leading to defective glucuronidation activity. This suggests that UGT1A9 poor metabolizer genotype(s) may be a predisposing factor for COMT inhibitor-induced hepatotoxicity.
Martignoni
E
E
Department of Clinical Medicine, University of Piemonte Orientale Amedeo Avogadro, Salvatore Maugeri Foundation, Scientific Institute of Veruno, Novara, Italy.
Cosentino
M
M
Ferrari
M
M
Porta
G
G
Mattarucchi
E
E
Marino
F
F
Lecchini
S
S
Nappi
G
G
D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects*; D001577:Benzophenones / Q000009:adverse effects; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury; D004252:DNA Mutational Analysis; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000378:metabolism; D005260:Female; D005838:Genotype; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D008107:Liver Diseases / Q000201:enzymology / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009570:Nitriles; D009596:Nitrophenols / Q000009:adverse effects; D010300:Parkinson Disease / Q000188:drug therapy; D011110:Polymorphism, Genetic / Q000235:genetics; D000077867:Tolcapone; D000090264:UDP-Glucuronosyltransferase 1A9
D000978:Antiparkinson Agents; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D005965:Glucuronates; D009570:Nitriles; D009596:Nitrophenols; C000715591:UGT1A9 protein, human; C071192:entacapone; D000077867:Tolcapone; D002394:Catechol O-Methyltransferase; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9