Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria

Scientific Reports
Flora S KanoTais N Sousa

Abstract

Malaria has provided a major selective pressure and has modulated the genetic diversity of the human genome. The variants of the Duffy Antigen/Receptor for Chemokines (DARC) gene have probably been selected by malaria parasites, particularly the FY*O allele, which is fixed in sub-Saharan Africa and confers resistance to Plasmodium vivax infection. Here, we showed the influence of genomic ancestry on the distribution of DARC genotypes in a highly admixed Brazilian population and confirmed the decreased susceptibility of the FY*A/FY*O genotype to clinical P. vivax malaria. FY*B/FY*O individuals were associated with a greater risk of developing clinical malaria. A remarkable difference among DARC variants concerning the susceptibility to clinical malaria was more evident for individuals who were less exposed to malaria, as measured by the time of residence in the endemic area. Additionally, we found that DARC-negative and FY*A/FY*O individuals had a greater chance of acquiring high levels of antibodies against the 19-kDa C-terminal region of the P. vivax merozoite surface protein-1. Altogether, our results provide evidence that DARC polymorphisms modulate the susceptibility to clinical P. vivax malaria and influence the naturally-...Continue Reading

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Citations

Jun 13, 2019·Genetics and Molecular Biology·Aracele Maria de SouzaCristiana Ferreira Alves de Brito
Feb 23, 2020·PLoS Pathogens·Jean PopoviciVirginie Rougeron
Mar 4, 2020·Antimicrobial Agents and Chemotherapy·Ana Carolina Rios SilvinoTais Nobrega Sousa
Oct 9, 2020·PLoS Computational Biology·Bridget S Penman, Sylvain Gandon
Jan 9, 2021·Journal of Physiological Anthropology·Shigeharu Sato
Nov 11, 2021·Journal of Bioinformatics and Computational Biology·Elena S GusarevaHie Lim Kim

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Methods Mentioned

BETA
PCR
Genotyping
Assay
enzyme-linked immunosorbent assay
ELISA
PCA

Software Mentioned

Epidata
R package pscl
DISTRUCT
R
R package cluster
SIVEP
Ade4
R package SNPassoc
Adegenet
Structure

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