A synonymous KCNH2 polymorphism and methadone trough level influence QTc prolongation in Kelantanese Malay recipients of methadone maintenance therapy (MMT) in Malaysia
-д хадгалсан:
| -д хэвлэсэн: | PLoS One vol. 20, no. 5 (May 2025), p. e0322724 |
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| Үндсэн зохиолч: | |
| Бусад зохиолчид: | , , , , |
| Хэвлэсэн: |
Public Library of Science
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| Нөхцлүүд: | |
| Онлайн хандалт: | Citation/Abstract Full Text Full Text - PDF |
| Шошгууд: |
Шошго байхгүй, Энэхүү баримтыг шошголох эхний хүн болох!
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MARC
| LEADER | 00000nab a2200000uu 4500 | ||
|---|---|---|---|
| 001 | 3200695396 | ||
| 003 | UK-CbPIL | ||
| 022 | |a 1932-6203 | ||
| 024 | 7 | |a 10.1371/journal.pone.0322724 |2 doi | |
| 035 | |a 3200695396 | ||
| 045 | 2 | |b d20250501 |b d20250531 | |
| 084 | |a 174835 |2 nlm | ||
| 100 | 1 | |a Muhammad Irfan Abdul Jalal | |
| 245 | 1 | |a A synonymous KCNH2 polymorphism and methadone trough level influence QTc prolongation in Kelantanese Malay recipients of methadone maintenance therapy (MMT) in Malaysia | |
| 260 | |b Public Library of Science |c May 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a Potassium voltage-gated channel subfamily H member 2 (KCNH2) polymorphisms have been found to influence the heart-rate adjusted QT (QTc) intervals. We investigated the association between KCNH2 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 KCNH2 polymorphisms: 1539C > T, 1956T > C, 2350C > T, and 2690A > C. Mean QTc interval is 408 ms (SD: 24). Molecular docking was performed on all four KCNH2 polymorphisms to investigate the impact of the nucleotide changes on methadone binding. Based on multiple regression analysis, only 1539T > C polymorphism (βadjusted: 10.506 (95% CI:0.846, 20.166), p = 0.033; recessive model), serum methadone trough (βadjusted: 0.025 (95% CI: 0.006, 0.043), p = 0.009), potassium (βadjusted: -8.756 (95% CI: -15.938, -1.575), p = 0.017) and magnesium (βadjusted: -106.226 (95% CI: -159.291, -53.161), p < 0.001) levels were significantly associated with mean QTc. Molecular docking analysis resulted in good binding-energy values between the 1539C > T and methadone, with the formation of hydrophobic and π–π stacking interactions, suggesting that 1539C > T was the newly discovered SNP involved in QTc prolongation. In conclusion, the 1539C > T KCNH2 polymorphism is associated with QTc prolongation in our MMT recipients, necessitating QTc monitoring to prevent methadone-associated cardiotoxicity in this Malay MMT population. | |
| 610 | 4 | |a Universiti Sains Malaysia | |
| 651 | 4 | |a Malaysia | |
| 651 | 4 | |a United States--US | |
| 653 | |a Magnesium | ||
| 653 | |a Drug withdrawal | ||
| 653 | |a Energy value | ||
| 653 | |a Electrocardiography | ||
| 653 | |a Maintenance | ||
| 653 | |a Binding | ||
| 653 | |a Heart rate | ||
| 653 | |a Regression analysis | ||
| 653 | |a EKG | ||
| 653 | |a Leukocytes | ||
| 653 | |a Potassium | ||
| 653 | |a Ethics | ||
| 653 | |a Intervals | ||
| 653 | |a Aggressive behavior | ||
| 653 | |a Drug dosages | ||
| 653 | |a Narcotics | ||
| 653 | |a Multiple regression analysis | ||
| 653 | |a Polymorphism | ||
| 653 | |a Sample size | ||
| 653 | |a Patient safety | ||
| 653 | |a Human immunodeficiency virus--HIV | ||
| 653 | |a Potassium channels (voltage-gated) | ||
| 653 | |a Nucleotides | ||
| 653 | |a Polymerase chain reaction | ||
| 653 | |a Molecular docking | ||
| 653 | |a Methadone | ||
| 653 | |a Genetic engineering | ||
| 653 | |a Single-nucleotide polymorphism | ||
| 653 | |a Channel gating | ||
| 653 | |a Peripheral blood | ||
| 653 | |a Cardiotoxicity | ||
| 653 | |a Methamphetamine | ||
| 653 | |a Prolongation | ||
| 653 | |a Hydrophobicity | ||
| 653 | |a Social | ||
| 700 | 1 | |a Abdullah-Zawawi, Muhammad-Redha | |
| 700 | 1 | |a Nurfadhlina Musa | |
| 700 | 1 | |a Ghazali, Basyirah | |
| 700 | 1 | |a Zahari, Zalina | |
| 700 | 1 | |a Nasir Mohamad | |
| 773 | 0 | |t PLoS One |g vol. 20, no. 5 (May 2025), p. e0322724 | |
| 786 | 0 | |d ProQuest |t Health & Medical Collection | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3200695396/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text |u https://www.proquest.com/docview/3200695396/fulltext/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3200695396/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |