{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:22:11Z","timestamp":1789420931091,"version":"build-2803163510"},"reference-count":51,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T00:00:00Z","timestamp":1380585600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["OMICS: A Journal of Integrative Biology"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in\n                    <jats:italic toggle=\"yes\">CYP2C19<\/jats:italic>\n                    gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    =0.021), and the Treatment Emergent Symptom Scale (TESS) total score (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    =0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the\n                    <jats:italic toggle=\"yes\">CYP2C19<\/jats:italic>\n                    SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    =0.035), and showed a lower plasma\n                    <jats:italic toggle=\"yes\">R<\/jats:italic>\n                    -methadone\/methadone dose ratio (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    =0.007) in urine opiate test negative patients, as well as a greater QTc change (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    =0.008) and higher total scores of TESS (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    =0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of\n                    <jats:italic toggle=\"yes\">CYP2C19<\/jats:italic>\n                    may potentially serve as an indicator for the plasma\n                    <jats:italic toggle=\"yes\">R<\/jats:italic>\n                    -methadone\/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations.\n                  <\/jats:p>","DOI":"10.1089\/omi.2012.0068","type":"journal-article","created":{"date-parts":[[2013,9,9]],"date-time":"2013-09-09T09:16:32Z","timestamp":1378718192000},"page":"519-526","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":35,"title":["Functional Genetic Polymorphisms in\n                    <i>CYP2C19<\/i>\n                    Gene in Relation to Cardiac Side Effects and Treatment Dose in a Methadone Maintenance Cohort"],"prefix":"10.1177","volume":"17","author":[{"given":"Sheng-Chang","family":"Wang","sequence":"first","affiliation":[{"name":"National Health Research Institutes","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ing-Kang","family":"Ho","sequence":"additional","affiliation":[{"name":"National Health 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