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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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-94679-7 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Gabrielly S. da Silva |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-86b0aeb4f51c4d8a9cf2a765bd7bfbe4 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-86b0aeb4f51c4d8a9cf2a765bd7bfbe42025-08-20T01:47:34ZengNature PortfolioScientific Reports2045-23222025-05-0115111010.1038/s41598-025-94679-7Impact of CYP2D6, MAOA, and UGT2B7 genetic variants on recurrence of Plasmodium Vivax in the Brazilian AmazonGabrielly S. da Silva0Flávia A. Fontenelle1Amanda O. Carvalho2Marielle M. Macêdo3Manuela C. Morais4Rebeca L. Abreu Netto5Victor I. Mwangi6Maria G. C. Alecrim7Marcus V. G. Lacerda8Fernanda Rodrigues-Soares9Anne C. G. de Almeida10Gisely Cardoso de Melo11Fundação de Medicina Tropical Doutor Heitor Vieira DouradoFundação de Medicina Tropical Doutor Heitor Vieira DouradoFundação de Medicina Tropical Doutor Heitor Vieira DouradoPrograma de Pós-Graduação em Ciências Aplicadas a Hematologia, Universidade do Estado do AmazonasFundação de Medicina Tropical Doutor Heitor Vieira DouradoFundação de Medicina Tropical Doutor Heitor Vieira DouradoFundação de Medicina Tropical Doutor Heitor Vieira DouradoFundação de Medicina Tropical Doutor Heitor Vieira DouradoFundação de Medicina Tropical Doutor Heitor Vieira DouradoDepartamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo MineiroFundação de Medicina Tropical Doutor Heitor Vieira DouradoFundação de Medicina Tropical Doutor Heitor Vieira DouradoAbstract 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.https://doi.org/10.1038/s41598-025-94679-7Plasmodium vivaxRecurrencesPrimaquineCYP2D6MAOAUGT2B7 |
| spellingShingle | 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 Impact of CYP2D6, MAOA, and UGT2B7 genetic variants on recurrence of Plasmodium Vivax in the Brazilian Amazon Scientific Reports Plasmodium vivax Recurrences Primaquine CYP2D6 MAOA UGT2B7 |
| title | Impact of CYP2D6, MAOA, and UGT2B7 genetic variants on recurrence of Plasmodium Vivax in the Brazilian Amazon |
| title_full | Impact of CYP2D6, MAOA, and UGT2B7 genetic variants on recurrence of Plasmodium Vivax in the Brazilian Amazon |
| title_fullStr | Impact of CYP2D6, MAOA, and UGT2B7 genetic variants on recurrence of Plasmodium Vivax in the Brazilian Amazon |
| title_full_unstemmed | Impact of CYP2D6, MAOA, and UGT2B7 genetic variants on recurrence of Plasmodium Vivax in the Brazilian Amazon |
| title_short | Impact of CYP2D6, MAOA, and UGT2B7 genetic variants on recurrence of Plasmodium Vivax in the Brazilian Amazon |
| title_sort | impact of cyp2d6 maoa and ugt2b7 genetic variants on recurrence of plasmodium vivax in the brazilian amazon |
| topic | Plasmodium vivax Recurrences Primaquine CYP2D6 MAOA UGT2B7 |
| url | https://doi.org/10.1038/s41598-025-94679-7 |
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