RESUMEN
Toll-like receptors (TLRs) play a key role in the induced immune response in malaria. Although the potential roles of TLRs have been described, it is necessary to elucidate which of these receptors may actually have an impact on the immunopathogenesis of the disease. This article performed a meta-analysis adhered to the PRISMA statement on TLRs studied in malaria by Plasmodium falciparum and Plasmodium vivax and its impact on susceptibility and pathogenesis during malaria. A search of the literature was undertaken in PubMed, LILACS and SciELO published until June 30th, 2020. The risk of bias was calculated using the Joanna Briggs Institute's Critical Review Checklist. Later, based on the inclusion and/or exclusion criteria, 17 out of 296 articles were harvested for this systematic review, the meta-analysis included studies incorporating 6,747 cases and 8,983 controls. The results showed that only TLR1, TLR9 and TLR4 receptors were associated with parasitemia, TLR2 and TLR6 were related with severity and none TLR was correlated with susceptibility. The data described here should be taken with caution, since the current evidence is limited and inconsistent. More studies are needed given that the results may change depending on the region and genetic background of the populations.
RESUMEN
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.