{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:02:51Z","timestamp":1787022171966,"version":"build-2736575974"},"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004595","name":"Universiti Sains Malaysia","doi-asserted-by":"publisher","award":["1001\/PPSP\/812056"],"award-info":[{"award-number":["1001\/PPSP\/812056"]}],"id":[{"id":"10.13039\/501100004595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Potassium voltage-gated channel subfamily H member 2 (\n                    <jats:italic>KCNH2<\/jats:italic>\n                    ) polymorphisms have been found to influence the heart-rate adjusted QT (QTc) intervals. We investigated the association between\n                    <jats:italic>KCNH2<\/jats:italic>\n                    polymorphisms and QTc intervals among Malay opioid-dependent methadone maintenance treatment (MMT) recipients. A cross-sectional study was conducted involving 111 patients with stable methadone dosage for at least 6 months attending several methadone clinics in Kelantan, Malaysia between March 2011 and October 2012. Those with cardiac structural defects, recipients of other QTc-prolonging pharmacotherapeutic agents, had aggressive behavior or other active psychiatric illnesses, chronic medical and surgical ailments and who were unable to communicate in Malay and English were excluded. The Fridericia-corrected QTc intervals were recorded using a 12-lead electrocardiogram. DNA samples were extracted from peripheral blood leukocytes and genotyped using nested allele-specific polymerase chain reaction for these four\n                    <jats:italic>KCNH2<\/jats:italic>\n                    polymorphisms: 1539C\u2009&gt;\u2009T, 1956T\u2009&gt;\u2009C, 2350C\u2009&gt;\u2009T, and 2690A\u2009&gt;\u2009C. Mean QTc interval is 408\u2009ms (SD: 24). Molecular docking was performed on all four\n                    <jats:italic>KCNH2<\/jats:italic>\n                    polymorphisms to investigate the impact of the nucleotide changes on methadone binding. Based on multiple regression analysis, only 1539T\u2009&gt;\u2009C polymorphism (\u03b2\n                    <jats:sub>adjusted<\/jats:sub>\n                    : 10.506 (95% CI:0.846, 20.166), p\u2009=\u20090.033; recessive model), serum methadone trough (\u03b2\n                    <jats:sub>adjusted<\/jats:sub>\n                    : 0.025 (95% CI: 0.006, 0.043), p\u2009=\u20090.009), potassium (\u03b2\n                    <jats:sub>adjusted<\/jats:sub>\n                    : -8.756 (95% CI: -15.938, -1.575), p\u2009=\u20090.017) and magnesium (\u03b2\n                    <jats:sub>adjusted<\/jats:sub>\n                    : -106.226 (95% CI: -159.291, -53.161), p\u2009&lt;\u20090.001) levels were significantly associated with mean QTc. Molecular docking analysis resulted in good binding-energy values between the 1539C\u2009&gt;\u2009T and methadone, with the formation of hydrophobic and \u03c0\u2013\u03c0 stacking interactions, suggesting that 1539C\u2009&gt;\u2009T was the newly discovered SNP involved in QTc prolongation. In conclusion, the 1539C\u2009&gt;\u2009T\n                    <jats:italic>KCNH2<\/jats:italic>\n                    polymorphism is associated with QTc prolongation in our MMT recipients, necessitating QTc monitoring to prevent methadone-associated cardiotoxicity in this Malay MMT population.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0322724","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T13:38:07Z","timestamp":1746452287000},"page":"e0322724","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["A synonymous KCNH2 polymorphism and methadone trough level influence QTc prolongation in Kelantanese Malay recipients of methadone maintenance therapy (MMT) in Malaysia"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6911-3335","authenticated-orcid":true,"given":"Muhammad Irfan","family":"Abdul Jalal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4404-6014","authenticated-orcid":true,"given":"Muhammad-Redha","family":"Abdullah-Zawawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7533-8474","authenticated-orcid":true,"given":"Nurfadhlina","family":"Musa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8129-7189","authenticated-orcid":true,"given":"Basyirah","family":"Ghazali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1459-8958","authenticated-orcid":true,"given":"Zalina","family":"Zahari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4370-1187","authenticated-orcid":true,"given":"Nasir","family":"Mohamad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"issue":"2","key":"pone.0322724.ref001","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.drugpo.2006.12.015","article-title":"Malaysia 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