{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:50:01Z","timestamp":1787014201858,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,1,20]],"date-time":"2019-01-20T00:00:00Z","timestamp":1547942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002738","name":"Assistance Publique - H\u00f4pitaux de Paris","doi-asserted-by":"publisher","award":["OST07013"],"award-info":[{"award-number":["OST07013"]}],"id":[{"id":"10.13039\/501100002738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["ASE07082KSA"],"award-info":[{"award-number":["ASE07082KSA"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Methadone is known to be a risk factor for sudden death by enlarging ECG QT corrected (QTc) interval. For other medical conditions, QTc lengthening has been described as the result of interactions between pharmacological treatments and genetic factors. Former heroin\u2010dependent subjects under methadone maintenance treatment in remission for at last 3\u00a0months were recruited. We studied the association between QTc length (Bazett formula) and 126 SNPs located on five genes (\n                    <jats:italic>KCNE1, KCNQ1, KCNH2, NOS1AP and SCN5A<\/jats:italic>\n                    ) previously associated with drug\u2010induced QT prolongation. Both SNP\u2010based and gene\u2010based approaches were used, and we tested also the interaction of the top SNP with methadone dosage to predict the QTc length. In our sample of 154 patients, current methadone daily dose was associated with QTc length (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>Pearson<\/jats:sub>\n                    <jats:italic>\u00a0=\u00a0<\/jats:italic>\n                    0.26;\n                    <jats:italic>P\u00a0=\u00a0<\/jats:italic>\n                    10\n                    <jats:sup>\u22123<\/jats:sup>\n                    ). Only one SNP, rs11911509 on\n                    <jats:italic>KCNE1,<\/jats:italic>\n                    remained significantly associated with QT length after correction for multiple testing (\n                    <jats:italic>P\u00a0=\u00a0<\/jats:italic>\n                    3.84\u00a0\u00d7\u00a010\n                    <jats:sup>\u22124<\/jats:sup>\n                    <jats:italic>; p<\/jats:italic>\n                    <jats:sub>corrected<\/jats:sub>\n                    <jats:italic>\u00a0=\u00a0<\/jats:italic>\n                    0.049). Using a gene\u2010based approach,\n                    <jats:italic>KCNE1<\/jats:italic>\n                    was also significantly associated with QTc length (\n                    <jats:italic>p<\/jats:italic>\n                    <jats:sub>empirical<\/jats:sub>\n                    \u00a0=\u00a00.02). We found a significant interaction between methadone dosage and rs11911509 minor allele count (allele A vs. C;\n                    <jats:italic>P\u00a0=\u00a0<\/jats:italic>\n                    0.01). Stratified analysis revealed that the correlation between QTc length and methadone dosage was restricted only to AA carriers of this top SNP. Patients\u2019 genetic background should be taken into account in the case of clinically relevant QT enlargement during methadone maintenance treatment.\n                  <\/jats:p>","DOI":"10.1111\/fcp.12405","type":"journal-article","created":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T15:30:32Z","timestamp":1533655832000},"page":"96-106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["QT length during methadone maintenance treatment: gene\u00a0\u00d7\u00a0dose interaction"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4965-2080","authenticated-orcid":false,"given":"El\u2010Hadi","family":"Zerdazi","sequence":"first","affiliation":[{"name":"INSERM U1144 Variabilit\u00e9 de r\u00e9ponse aux psychotropes Universit\u00e9 Paris Descartes Universit\u00e9 Paris Diderot Universit\u00e9 Sorbonne Paris Cit\u00e9 Facult\u00e9 de Pharmacie 4 avenue de l'observatoire \u2010 75006 Paris France"},{"name":"APHP Service d'addictologie DHU Pe\u2010PSY P\u00f4le de Psychiatrie et d'Addictologie des H\u00f4pitaux Universitaires Henri Mondor F94000 Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5168-3727","authenticated-orcid":false,"given":"Florence","family":"Vorspan","sequence":"additional","affiliation":[{"name":"INSERM U1144 Variabilit\u00e9 de r\u00e9ponse aux psychotropes Universit\u00e9 Paris Descartes Universit\u00e9 Paris Diderot Universit\u00e9 Sorbonne Paris Cit\u00e9 Facult\u00e9 de Pharmacie 4 avenue de l'observatoire \u2010 75006 Paris France"},{"name":"APHP D\u00e9partement de Psychiatrie et de M\u00e9decine Addictologigue H\u00f4pital Fernand Widal 75010 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andries T.","family":"Marees","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Amsterdam Neuroscience Academic Medical Center 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