Pharmacogenetic analysis of adverse drug effect reveals genetic variant for susceptibility to liver toxicity.
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| Abstract |
A retrospective pharmacogenetic study was conducted to identify possible genetic susceptibility factors in patients in whom the administration of the anti-Parkinson drug, tolcapone (TASMAR), was associated with hepatic toxicity. We studied 135 cases of patients with elevated liver transaminase levels (ELT) of >/=1.5 times above the upper limit of normal, in comparison with matched controls that had also received the drug but had not experienced ELT. DNA samples were genotyped for 30 previously described or newly characterized bi-allelic single nucleotide polymorphisms (SNPs), representing 12 candidate genes selected based on the known metabolic pathways involved in the tolcapone elimination. SNPs located within the UDP-glucuronosyl transferase 1A gene complex, which codes for the enzymes involved in the main elimination pathway of the drug, were found to be significantly associated with the occurrence of tolcapone-associated ELTs.
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| Authors | Gonzalo Acuña, Dorothee Foernzler, Diane Leong, Michael Rabbia, Ralf Smit, Ernest Dorflinger, Rodolfo Gasser, Josephine Hoh, Jürg Ott, Edilio Borroni, Zung To, Annick Thompson, Jia Li, Lara Hashimoto, Klaus Lindpaintner |
| Journal | The pharmacogenomics journal (Pharmacogenomics J) Vol. 2 Issue 5 Pg. 327-34 ( 2002) ISSN: 1470-269X [Print] United States |
| PMID | 12439739 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
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