da Silva Gabrielly S, Fontenelle Flávia A, Carvalho Amanda O, Macêdo Marielle M, Morais Manuela C, Abreu Netto Rebeca L, Mwangi Victor I, Alecrim Maria G C, Lacerda Marcus V G, Rodrigues-Soares Fernanda, de Almeida Anne C G, de Melo Gisely Cardoso
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, AM, 69040-000, Brazil.
Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, AM, 69040-000, Brazil.
Sci Rep. 2025 May 2;15(1):15330. doi: 10.1038/s41598-025-94679-7.
The biotransformation of primaquine is mediated by cytochrome P-450 (CYP) enzymes and monoamine oxygenase A (MAO-A). Polymorphisms in the genes that encode these enzymes can alter the clinical response of patients with Plasmodium vivax malaria, leading to therapeutic failure and recurrences. This study aimed to investigate the influence of variations in CYP2D6, MAOA, and UGT2B7 genes on recurrences of vivax malaria. In this case-control study, 72 individuals with vivax malaria were divided into two groups: 18 recurrences and 54 non-recurrences cases. Genotyping of CYP2D6, MAOA, and UGT2B7 was performed using a TaqMan assay and Real-time PCR. The frequency of CYP2D6 alleles was similar between the groups, except for the reduced-function allele *4, which was more frequent in the recurrence group (p = 0.019). Furthermore, the CYP2D6 normal metabolizers (gNM) phenotype had a higher frequency in individuals without recurrence (p = 0.039). An association was found between mutated MAOA genotypes (CC + CT) and a shorter time to recurrence compared to the wild-type (p = 0.0437). However, no association was found between UGT2B7 genotypes and recurrence. These findings suggest that genetic variations in both CYP2D6 and MAOA may contribute to the therapeutic failure of primaquine, reinforcing the importance of pharmacogenetics in monitoring antimalarial therapies.
伯氨喹的生物转化由细胞色素P-450（CYP）酶和单胺氧化酶A（MAO-A）介导。编码这些酶的基因中的多态性可改变间日疟原虫疟疾患者的临床反应，导致治疗失败和复发。本研究旨在调查CYP2D6、MAOA和UGT2B7基因变异对间日疟复发的影响。在这项病例对照研究中，72例间日疟患者被分为两组：18例复发患者和54例未复发患者。使用TaqMan分析和实时PCR对CYP2D6、MAOA和UGT2B7进行基因分型。除功能降低的等位基因*4外，两组间CYP2D6等位基因频率相似，*4在复发组中更常见（p = 0.019）。此外，CYP2D6正常代谢者（gNM）表型在未复发个体中的频率更高（p = 0.039）。与野生型相比，发现突变的MAOA基因型（CC + CT）与较短的复发时间相关（p = 0.0437）。然而，未发现UGT2B7基因型与复发之间存在关联。这些发现表明，CYP2D6和MAOA的基因变异可能导致伯氨喹治疗失败，强化了药物遗传学在监测抗疟治疗中的重要性。
