Abstract
Genetic variability was linked with individual responses to treatment and susceptibility to malaria by Plasmodium vivax. Polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatment. The aim of the study was to investigate whether or not CYP2D6 single nucleotide polymorphisms rs1065852, rs38920-97, rs16947 and rs28371725 are unequally distributed in malaria by Plasmodium vivax individuals from the Brazilian Amazon region. The blood samples were collected from 220 unrelated Plasmodium vivax patients from five different endemic areas. Genotyping was performed using SNaPshot® and real-time polymerase chain reaction methods. In all five areas, the rs1065852 (CYP2D6*10, C.100C > T), rs3892097 (CYP2D6*4, 1846C > T) and rs16947 (CYP2D6*2, C.2850G > A), as a homozygous genotype, showed the lowest frequencies. The rs28371725 (CYP2D6*41, 2988G > A) homozygous genotype was not detected, while the allele A was found in a single patient from Macapá region. No deviations from Hardy-Weinberg equilibrium were found, although a borderline p-value was observed (p = 0.048) for the SNP rs3892097 in Goianésia do Pará, Pará state. No significant associations were detected in these frequencies among the five studied areas. For the SNP rs3892097, a higher frequency was observed for the C/T heterozygous genotype in the Plácido de Castro and Macapá, Acre and Amapá states, respectively. The distribution of the CYP2D6 alleles investigated in the different areas of the Brazilian Amazon is not homogeneous. Further investigations are necessary in order to determine which alleles might be informative to assure optimal drug dosing recommendations based on experimental pharmacogenetics.
Highlights
Malaria transmission in Brazil is described to hypo-mesoendemic, unstable and with annual seasonal variations (Oliveira-Ferreira et al, 2010)
The patients enrolled in this study complied with the following criteria: they presented clinical malaria symptoms and sought medical assistance, were over 18 years old and had positive results by microscopy, and infection with P. vivax was subsequently confirmed by nested polymerase chain reaction (PCR), followed by signed written informed consent forms
One of the main treatment challenges in P. vivax malaria is to achieve an effective and safe radical cure for the patient, since the frequent relapse episodes, caused by activation of hypnozoites, are extremely difficult to control due to the absence of biomarkers for diagnosis and detection of latent forms (Brasil et al, 2018)
Summary
Malaria transmission in Brazil is described to hypo-mesoendemic, unstable and with annual seasonal variations (Oliveira-Ferreira et al, 2010). Plasmodium vivax was responsible for more than 14.3 million malaria cases in the world and 50% of all malaria cases outside the African continent (Battle et al, 2019). P. vivax malaria is an important public health issue in Brazil, and it accounts for approximately 89% of clinical cases reported annually (Brasil et al, 2017). The Brazilian National Malaria Control Program provides guidelines for treatment and provides free antimalarials. The variability of Plasmodium response to antimalarials limits therapeutic success. Other factors including those intrinsic to the host, the parasite and the antimalarials as well as their interactions contribute to treatment failure (Baird, 2009)
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