| http://purl.uniprot.org/citations/30118797 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30118797 | http://www.w3.org/2000/01/rdf-schema#comment | "Bosentan, an endothelin receptor antagonist, has been widely used as a first-line drug for the treatment of pulmonary arterial hypertension (PAH). In addition, bosentan is approved for patients with digital ulcers related to systemic sclerosis. Liver dysfunction is a major adverse effect of bosentan and may lead to discontinuation of therapy. The purpose of this study was to identify genomic biomarkers to predict bosentan-induced liver injury. A total of 69 PAH patients were recruited into the study. An exploratory analysis of 1936 single-nucleotide polymorphisms (SNPs) in 231 genes involved in absorption, distribution, metabolism, and elimination of multiple medications using Affimetrix DMET™ (Drug Metabolism Enzymes and Transporters) chips was performed. We extracted 16 SNPs (P < 0.05) using the Jonckheere-Terpstra trend test and multiplex logistic analysis; we identified two SNPs in two genes, CHST3 and CHST13, which are responsible for proteoglycan sulfation and were significantly associated with bosentan-induced liver injury. We constructed a predictive model for bosentan-induced liver injury (area under the curve [AUC]: 0.89, sensitivity: 82.61%, specificity: 86.05%) via receiver operating curve (ROC) analysis using 2 SNPs and 2 non-genetic factors. Two SNPs were identified as potential predictive markers for bosentan-induced liver injury in Japanese patients with pulmonary arterial hypertension. This is the first pharmacogenomics study linking proteoglycan sulfating genes to drug-induced liver dysfunction, a frequently observed clinical adverse effect of bosentan therapy. These results may provide a way to personalize PAH medicine as well as provide novel mechanistic insights to drug-induced liver dysfunction."xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.phrs.2018.08.011"xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/author | "Nakayama K."xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/author | "Suzuki Y."xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/author | "Hirata K.I."xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/author | "Kumagai S."xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/author | "Miyagawa K."xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/author | "Uemura Y."xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/author | "Emoto N."xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/author | "Tsuji G."xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/author | "Yorifuji K."xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/author | "Horibata S."xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/name | "Pharmacol Res"xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/pages | "259-264"xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/title | "CHST3 and CHST13 polymorphisms as predictors of bosentan-induced liver toxicity in Japanese patients with pulmonary arterial hypertension."xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://purl.uniprot.org/core/volume | "135"xsd:string |
| http://purl.uniprot.org/citations/30118797 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/30118797 |
| http://purl.uniprot.org/citations/30118797 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/30118797 |
| http://purl.uniprot.org/uniprot/#_Q3ZCR4-mappedCitation-30118797 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30118797 |
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| http://purl.uniprot.org/uniprot/#_Q7LGC8-mappedCitation-30118797 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30118797 |
| http://purl.uniprot.org/uniprot/#_Q8NET6-mappedCitation-30118797 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30118797 |
| http://purl.uniprot.org/uniprot/Q3ZCR4 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/30118797 |