Detalhes bibliográficos
| Título: |
A synonymous KCNH2 polymorphism and methadone trough level influence QTc prolongation in Kelantanese Malay recipients of methadone maintenance therapy (MMT) in Malaysia. |
| Autores: |
Abdul Jalal, Muhammad Irfan1 (AUTHOR) irfan.abduljalal@ukm.edu.my, Abdullah-Zawawi, Muhammad-Redha1 (AUTHOR), Musa, Nurfadhlina2 (AUTHOR), Ghazali, Basyirah3 (AUTHOR), Zahari, Zalina4 (AUTHOR), Mohamad, Nasir5 (AUTHOR) |
| Fonte: |
PLoS ONE. 5/5/2025, Vol. 20 Issue 5, p1-22. 22p. |
| Termos do Assunto: |
*METHADONE treatment programs, *MULTIPLE regression analysis, *GENETIC polymorphisms, *POLYMERASE chain reaction, *STACKING interactions |
| Resumo: |
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. [ABSTRACT FROM AUTHOR] |
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