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

Sci Rep. 2025 May 2;15(1):15330. doi: 10.1038/s41598-025-94679-7.

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.

Keywords: CYP2D6; MAOA; Plasmodium vivax; UGT2B7; Primaquine; Recurrences.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Antimalarials / therapeutic use
  • Brazil / epidemiology
  • Case-Control Studies
  • Cytochrome P-450 CYP2D6* / genetics
  • Female
  • Gene Frequency
  • Genotype
  • Glucuronosyltransferase* / genetics
  • Humans
  • Malaria, Vivax* / drug therapy
  • Malaria, Vivax* / epidemiology
  • Malaria, Vivax* / genetics
  • Malaria, Vivax* / parasitology
  • Male
  • Middle Aged
  • Monoamine Oxidase* / genetics
  • Plasmodium vivax*
  • Polymorphism, Single Nucleotide
  • Primaquine / therapeutic use
  • Recurrence
  • Young Adult

Substances

  • Cytochrome P-450 CYP2D6
  • Glucuronosyltransferase
  • UGT2B7 protein, human
  • Monoamine Oxidase
  • Primaquine
  • monoamine oxidase A, human
  • Antimalarials