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Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian Amazon
BACKGROUND: In malaria infection, apoptosis acts as an important immunomodulatory mechanism that leads to the elimination of parasitized cells, thus reducing the parasite density and controlling immune cell populations. Here, it was investigated the association of INDEL variants in apoptotic genes—r...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552311/ https://www.ncbi.nlm.nih.gov/pubmed/37794476 http://dx.doi.org/10.1186/s12936-023-04729-6 |
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author | Sena-dos-Santos, Camille Cavalcante, Giovanna C. Marques, Diego Silva, Caio S. de Moraes, Milene Raiol Pinto, Pablo Santana-da-Silva, Mayara Natália Ferraz, Rafaella S. Costa, Sheyla Patrícia T. Ventura, Ana Maria R. Póvoa, Marinete M. Cunha, Maristela G. Ribeiro-dos-Santos, Ândrea |
author_facet | Sena-dos-Santos, Camille Cavalcante, Giovanna C. Marques, Diego Silva, Caio S. de Moraes, Milene Raiol Pinto, Pablo Santana-da-Silva, Mayara Natália Ferraz, Rafaella S. Costa, Sheyla Patrícia T. Ventura, Ana Maria R. Póvoa, Marinete M. Cunha, Maristela G. Ribeiro-dos-Santos, Ândrea |
author_sort | Sena-dos-Santos, Camille |
collection | PubMed |
description | BACKGROUND: In malaria infection, apoptosis acts as an important immunomodulatory mechanism that leads to the elimination of parasitized cells, thus reducing the parasite density and controlling immune cell populations. Here, it was investigated the association of INDEL variants in apoptotic genes—rs10562972 (FAS), rs4197 (FADD), rs3834129 and rs59308963 (CASP8), rs61079693 (CASP9), rs4647655 (CASP3), rs11269260 (BCL-2), and rs17880560 (TP53)—and the influence of genetic ancestry with susceptibility to malaria and parasite density in an admixed population from the Brazilian Amazon. METHODS: Total DNA was extracted from 126 malaria patients and 101 uninfected individuals for investigation of genetic ancestries and genotypic distribution of apoptosis-related variants by Multiplex PCR. Association analyses consisted of multivariate logistic regressions, considering the following comparisons: (i) DEL/DEL genotype vs. INS/DEL + INS/INS; and (ii) INS/INS vs. INS/DEL + DEL/DEL. RESULTS: Individuals infected by Plasmodium falciparum had significantly higher African ancestry proportions in comparison to uninfected controls, Plasmodium vivax, and mixed infections. The INS/INS genotype of rs3834129 (CASP8) seemed to increase the risk for P. falciparum infection (P = 0.038; OR = 1.867; 95% CI 0.736–3.725), while the DEL/DEL genotype presented a significant protective effect against infection by P. falciparum (P = 0.049; OR = 0.446; 95% CI 0.185–0.944) and mixed infection (P = 0.026; OR = 0.545; 95% CI 0.281–0.996), and was associated with lower parasite density in P. falciparum malaria (P = 0.009; OR = 0.383; 95% CI 0.113–1.295). Additionally, the INS/INS genotype of rs10562972 (FAS) was more frequent among individuals infected with P. vivax compared to P. falciparum (P = 0.036; OR = 2.493; 95% CI 1.104–4.551), and the DEL/DEL genotype of rs17880560 (TP53) was significantly more present in patients with mono-infection by P. vivax than in individuals with mixed infection (P = 0.029; OR = 0.667; 95% CI 0.211–1.669). CONCLUSIONS: In conclusion, variants in apoptosis genes are associated with malaria susceptibility and parasite density, indicating the role of apoptosis-related genetic profiles in immune responses against malaria infection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12936-023-04729-6. |
format | Online Article Text |
id | pubmed-10552311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-105523112023-10-06 Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian Amazon Sena-dos-Santos, Camille Cavalcante, Giovanna C. Marques, Diego Silva, Caio S. de Moraes, Milene Raiol Pinto, Pablo Santana-da-Silva, Mayara Natália Ferraz, Rafaella S. Costa, Sheyla Patrícia T. Ventura, Ana Maria R. Póvoa, Marinete M. Cunha, Maristela G. Ribeiro-dos-Santos, Ândrea Malar J Research BACKGROUND: In malaria infection, apoptosis acts as an important immunomodulatory mechanism that leads to the elimination of parasitized cells, thus reducing the parasite density and controlling immune cell populations. Here, it was investigated the association of INDEL variants in apoptotic genes—rs10562972 (FAS), rs4197 (FADD), rs3834129 and rs59308963 (CASP8), rs61079693 (CASP9), rs4647655 (CASP3), rs11269260 (BCL-2), and rs17880560 (TP53)—and the influence of genetic ancestry with susceptibility to malaria and parasite density in an admixed population from the Brazilian Amazon. METHODS: Total DNA was extracted from 126 malaria patients and 101 uninfected individuals for investigation of genetic ancestries and genotypic distribution of apoptosis-related variants by Multiplex PCR. Association analyses consisted of multivariate logistic regressions, considering the following comparisons: (i) DEL/DEL genotype vs. INS/DEL + INS/INS; and (ii) INS/INS vs. INS/DEL + DEL/DEL. RESULTS: Individuals infected by Plasmodium falciparum had significantly higher African ancestry proportions in comparison to uninfected controls, Plasmodium vivax, and mixed infections. The INS/INS genotype of rs3834129 (CASP8) seemed to increase the risk for P. falciparum infection (P = 0.038; OR = 1.867; 95% CI 0.736–3.725), while the DEL/DEL genotype presented a significant protective effect against infection by P. falciparum (P = 0.049; OR = 0.446; 95% CI 0.185–0.944) and mixed infection (P = 0.026; OR = 0.545; 95% CI 0.281–0.996), and was associated with lower parasite density in P. falciparum malaria (P = 0.009; OR = 0.383; 95% CI 0.113–1.295). Additionally, the INS/INS genotype of rs10562972 (FAS) was more frequent among individuals infected with P. vivax compared to P. falciparum (P = 0.036; OR = 2.493; 95% CI 1.104–4.551), and the DEL/DEL genotype of rs17880560 (TP53) was significantly more present in patients with mono-infection by P. vivax than in individuals with mixed infection (P = 0.029; OR = 0.667; 95% CI 0.211–1.669). CONCLUSIONS: In conclusion, variants in apoptosis genes are associated with malaria susceptibility and parasite density, indicating the role of apoptosis-related genetic profiles in immune responses against malaria infection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12936-023-04729-6. BioMed Central 2023-10-04 /pmc/articles/PMC10552311/ /pubmed/37794476 http://dx.doi.org/10.1186/s12936-023-04729-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Sena-dos-Santos, Camille Cavalcante, Giovanna C. Marques, Diego Silva, Caio S. de Moraes, Milene Raiol Pinto, Pablo Santana-da-Silva, Mayara Natália Ferraz, Rafaella S. Costa, Sheyla Patrícia T. Ventura, Ana Maria R. Póvoa, Marinete M. Cunha, Maristela G. Ribeiro-dos-Santos, Ândrea Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian Amazon |
title | Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian Amazon |
title_full | Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian Amazon |
title_fullStr | Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian Amazon |
title_full_unstemmed | Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian Amazon |
title_short | Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian Amazon |
title_sort | association of apoptosis-related variants to malaria infection and parasite density in individuals from the brazilian amazon |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552311/ https://www.ncbi.nlm.nih.gov/pubmed/37794476 http://dx.doi.org/10.1186/s12936-023-04729-6 |
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