Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria
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 Af...
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doaj-33cfd9ed40a8459583acd20767c13c782020-12-08T03:54:32ZengNature Publishing GroupScientific Reports2045-23222018-09-018111410.1038/s41598-018-32254-zSusceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malariaFlora Satiko Kano0Aracele Maria de Souza1Leticia de Menezes Torres2Marcelo Azevedo Costa3Flávia Alessandra Souza-Silva4Bruno Antônio Marinho Sanchez5Cor Jesus Fernandes Fontes6Irene Silva Soares7Cristiana Ferreira Alves de Brito8Luzia Helena Carvalho9Tais Nobrega Sousa10Molecular Biology and Malaria Immunology Research Group, Instituto René Rachou, Fundação Oswaldo Cruz (FIOCRUZ)Molecular Biology and Malaria Immunology Research Group, Instituto René Rachou, Fundação Oswaldo Cruz (FIOCRUZ)Molecular Biology and Malaria Immunology Research Group, Instituto René Rachou, Fundação Oswaldo Cruz (FIOCRUZ)Departamento de Engenharia de Produção, Universidade Federal de Minas GeraisMolecular Biology and Malaria Immunology Research Group, Instituto René Rachou, Fundação Oswaldo Cruz (FIOCRUZ)Universidade Federal de Mato GrossoHospital Julio Muller, Universidade Federal de Mato GrossoDepartamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São PauloMolecular Biology and Malaria Immunology Research Group, Instituto René Rachou, Fundação Oswaldo Cruz (FIOCRUZ)Molecular Biology and Malaria Immunology Research Group, Instituto René Rachou, Fundação Oswaldo Cruz (FIOCRUZ)Molecular Biology and Malaria Immunology Research Group, Instituto René Rachou, Fundação Oswaldo Cruz (FIOCRUZ)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-acquired humoral immune response to malaria blood antigens, which may interfere with the efficacy of a future vaccine against malaria.https://doi.org/10.1038/s41598-018-32254-zDuffy Antigen Receptor For Chemokines (DARC)Vivax MalariaGenomic AncestryClinical MalariaAncestry Informative Markers (AIMs) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Flora Satiko Kano Aracele Maria de Souza Leticia de Menezes Torres Marcelo Azevedo Costa Flávia Alessandra Souza-Silva Bruno Antônio Marinho Sanchez Cor Jesus Fernandes Fontes Irene Silva Soares Cristiana Ferreira Alves de Brito Luzia Helena Carvalho Tais Nobrega Sousa |
spellingShingle |
Flora Satiko Kano Aracele Maria de Souza Leticia de Menezes Torres Marcelo Azevedo Costa Flávia Alessandra Souza-Silva Bruno Antônio Marinho Sanchez Cor Jesus Fernandes Fontes Irene Silva Soares Cristiana Ferreira Alves de Brito Luzia Helena Carvalho Tais Nobrega Sousa Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria Scientific Reports Duffy Antigen Receptor For Chemokines (DARC) Vivax Malaria Genomic Ancestry Clinical Malaria Ancestry Informative Markers (AIMs) |
author_facet |
Flora Satiko Kano Aracele Maria de Souza Leticia de Menezes Torres Marcelo Azevedo Costa Flávia Alessandra Souza-Silva Bruno Antônio Marinho Sanchez Cor Jesus Fernandes Fontes Irene Silva Soares Cristiana Ferreira Alves de Brito Luzia Helena Carvalho Tais Nobrega Sousa |
author_sort |
Flora Satiko Kano |
title |
Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria |
title_short |
Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria |
title_full |
Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria |
title_fullStr |
Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria |
title_full_unstemmed |
Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria |
title_sort |
susceptibility to plasmodium vivax malaria associated with darc (duffy antigen) polymorphisms is influenced by the time of exposure to malaria |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2018-09-01 |
description |
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-acquired humoral immune response to malaria blood antigens, which may interfere with the efficacy of a future vaccine against malaria. |
topic |
Duffy Antigen Receptor For Chemokines (DARC) Vivax Malaria Genomic Ancestry Clinical Malaria Ancestry Informative Markers (AIMs) |
url |
https://doi.org/10.1038/s41598-018-32254-z |
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