A synonymous KCNH2 polymorphism and methadone trough level influence QTc prolongation in Kelantanese Malay recipients of methadone maintenance therapy (MMT) in Malaysia

Muhammad Irfan Abdul Jalal, Muhammad-Redha Abdullah-Zawawi, Nurfadhlina Musa, Basyirah Ghazali, Zalina Zahari and Nasir Mohamad

PLOS ONE, 2025, vol. 20, issue 5, 1-22

Abstract: 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 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0322724 (text/html)
https://journals.plos.org/plosone/article/file?id= ... 22724&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0322724

DOI: 10.1371/journal.pone.0322724

Access Statistics for this article

More articles in PLOS ONE from Public Library of Science
Bibliographic data for series maintained by plosone ().