Impact of CYP2D6, MAOA, and UGT2B7 genetic variants on recurrence of Plasmodium Vivax in the Brazilian Amazon

Impact of CYP2D6, MAOA, and UGT2B7 genetic variants on recurrence of Plasmodium Vivax in the Brazilian Amazon

Abstract 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...

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Main Authors: Gabrielly S. da Silva, Flávia A. Fontenelle, Amanda O. Carvalho, Marielle M. Macêdo, Manuela C. Morais, Rebeca L. Abreu Netto, Victor I. Mwangi, Maria G. C. Alecrim, Marcus V. G. Lacerda, Fernanda Rodrigues-Soares, Anne C. G. de Almeida, Gisely Cardoso de Melo
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
Subjects:
Plasmodium vivax
Recurrences
Primaquine
CYP2D6
MAOA
UGT2B7
Online Access:https://doi.org/10.1038/s41598-025-94679-7
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Summary:Abstract 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.
ISSN:2045-2322

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