FY polymorphisms and vivax malaria in inhabitants of Amazonas State, Brazil

Abstract

Although the importance of glycoprotein Duffy in the human red cells invasion process by Plasmodium vivax merozoites has been demonstrated, little is known about the associations of FY polymorphisms with malaria vivax parasitic density. In this study, we investigated the associations of the SNPs 125 G>A, 265 C>T, and 298 G>A on FY gene and the SNP -33T>C on GATA box with the vivax malaria parasitic density in inhabitants of Amazon State, Brazil. Verifications of P. vivax, as well as the definition of parasitism, were determined by standard screening tests in 497 patients. FY phenotyping was performed in all samples by hemagglutination using gel cards. Molecular analysis for FY/GATA polymorphisms were performed by polymerase chain reaction-restriction fragment length polymorphism. Our data showed that in this population, FY*A/FY*B-33 and FY*B/FY*B-33 genotypes may be a selective advantage, reducing the frequency of P. vivax infection in the studied area. FY*A/FY*B and FY*A/FY*A genotypes showed to be associated with the rise of the frequency of P. vivax infection, and FY*B/FY*X and FY*A/FY*X showed to be associated with the low levels of parasitism. These results suggest that natural adaptations, in malaria-endemic regions, could be leading to the arising of partial defense mechanisms against P. vivax, which is different from the previously described in African descents, as well as adaptations that could be increasing the susceptibility of human to this kind of malaria.

Potential Immune Mechanisms Associated with Anemia in Plasmodium vivax Malaria: a Puzzling Question

“…It is well established that P. vivax endemicity and estimates of populations at risk are strongly influenced by the proportion of Duffy antigen-negative individuals relatively refractory to the P. vivax infection (4,68). FY*B/FY*X and FY*A/FY*X genotypes are associated with low parasite density, which may favorably impact hemoglobin levels (69). Observational studies have shown protection against P. vivax infections conferred by a RBC enzyme (glucose-6-phosphate dehydrogenase) deficiency (70)(71)(72) and an erythrocyte membrane disorder (Southeast Asian ovalocytosis) by a mechanism that is independent of the Duffy antigen (73).…”

Population Genetic Analysis of the DARC Locus (Duffy) Reveals Adaptation from Standing Variation Associated with Malaria Resistance in Humans

“…We also compared extended haplotype homozygosity (EHH) [55] and integrated haplotype score (iHH) [29] in the region for each of the three allelic classes (S1 Fig), [12,18,19,21]. Despite this debate, it exhibits strong population differentiation and structure.…”

“…Individuals with the FY Ã O allele do not express the Duffy receptor in red blood cells resulting in immunity to P.vivax [6,10] and individuals with the FY Ã A allele may have lower infectivity rates [11,12,[18][19][20][21]. Unlike P. falciparum, the most common and deadly malaria protozoan in Africa that uses multiple entry receptors, P.vivax's one mode of entry allows the possibility of resistance with only one SNP.…”

“…It has been proposed that due to the near-fixation of FY Ã O, P. vivax infection in humans is largely absent from equatorial Africa. An important recent discovery suggests low levels of P.vivax infection in FY Ã O homozygotes [13][14][15][16][17], which indicates that P. vivax might be evolving escape variants able to overcome the protective effect of FY Ã O. Phenotypic effects of the FY Ã A mutation are less clear than FY Ã O; however, there is evidence of natural selection and reduced P. vivax infection in individuals with this genotype ( [18,19], with conflicting reports in the Brazilian Amazon however [12,20,21]). …”

A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines

“…The material loaded in the lanes is identical to that in the silver nitrate stained gel except that lane 1 contains an aliquot of red blood cells membrane lysate human red blood cells by P.vivax, indeed it has been already suggested that Duffy antigen inhibitors might be useful therapeutic agents for P. vivax malaria [70]. However, recent data suggest that P.vivax has shortcut its absolute dependency on DARC to invade red blood cells [19][20][21], even if it is still believed to be the main entry route, as suggested by the inverse correlation of P. vivax malaria severity with expression level of DARC on red cells [71,72]. One can observe mixed infections with more than one species of Plasmodium in one single individual; coexistence of diverse Plasmodium species infecting populations living in the same area is also frequently encountered.…”