AUTHOR=Cardoso Jaiana L. M. , Salazar Yanka E. A. R. , Almeida Anne C. G. , Barbosa Laila R. A. , Silva Emanuelle L. , Rodrigues Maria Gabriela Almeida , Rodrigues-Soares Fernanda , Sampaio Vanderson S. , Siqueira André M. , Lacerda Marcus V. G. , Monteiro Wuelton M. , Melo Gisely C. 

TITLE=Influence of CYP2D6, CYP3A4 and CYP2C19 Genotypes on Recurrence of Plasmodium vivax

JOURNAL=Frontiers in Tropical Diseases

VOLUME=3

YEAR=2022

URL=https://www.frontiersin.org/journals/tropical-diseases/articles/10.3389/fitd.2022.845451

DOI=10.3389/fitd.2022.845451

ISSN=2673-7515

ABSTRACT=<sec><title>Background</title><p>The influence of the CYPs (cytochrome P-450) in the success of antimalarial therapy remains uncertain. In this study, the association of <italic>CYP2D6, CYP2C19</italic> and <italic>CYP3A4</italic> polymorphisms and predicted phenotypes with malaria recurrence was investigated.</p></sec><sec><title>Methods</title><p>After diagnosis of vivax malaria, individuals treated at a reference center in Manaus were followed up for 180 days. Patients were separated into two groups: a recurrence group and a non-recurrence group. Genotyping of <italic>CYP2D6, CYP2C19</italic> and <italic>CYP3A4</italic> was performed using a TaqMan™ assay and real-time PCR.</p></sec><sec><title>Findings</title><p>The frequencies of decreased-function and normal-function alleles and phenotypes for all CYPs were similar between the groups, except for the <italic>CYP2D6</italic>*2xN allele (p=0.047) and the <italic>CYP2D6</italic> gUM phenotype (p=0.057), which were more frequent in individuals without recurrence. Despite this, the <italic>CYP2D6</italic>, <italic>CYP2C19</italic> and <italic>CYP3A4</italic> genotypes had no association with an increased risk of recurrence. CYPs polymorphisms also had no influence in parasite clearance, neither in the time nor the number of recurrence episodes. MAIN</p></sec><sec><title>Conclusion</title><p>This prospective cohort study demonstrated that <italic>CYP2D6</italic>, <italic>CYP2C19</italic> and <italic>CYP3A4</italic> polymorphisms have no influence on malaria recurrence. Nonetheless, our findings suggest that the <italic>CYP2D6</italic> predicted ultrarapid phenotype was less susceptible to recurrence, and that patients with the <italic>CYP2D6</italic> gUM phenotype are less susceptible to primaquine failure. Additional investigation of pharmacogenetics and pharmacokinetics are needed before implementing CYP analysis to better orientate individualized radical treatment of vivax malaria in reference centers that treat patients with multiple recurrences.</p></sec>