Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian Amazon
Abstract 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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-023-04729-6 |
| _version_ | 1827724485756715008 |
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| author | Camille Sena-dos-Santos Giovanna C. Cavalcante Diego Marques Caio S. Silva Milene Raiol de Moraes Pablo Pinto Mayara Natália Santana-da-Silva Rafaella S. Ferraz Sheyla Patrícia T. Costa Ana Maria R. Ventura Marinete M. Póvoa Maristela G. Cunha Ândrea Ribeiro-dos-Santos |
| author_facet | Camille Sena-dos-Santos Giovanna C. Cavalcante Diego Marques Caio S. Silva Milene Raiol de Moraes Pablo Pinto Mayara Natália Santana-da-Silva Rafaella S. Ferraz Sheyla Patrícia T. Costa Ana Maria R. Ventura Marinete M. Póvoa Maristela G. Cunha Ândrea Ribeiro-dos-Santos |
| author_sort | Camille Sena-dos-Santos |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-10T22:16:27Z |
| format | Article |
| id | doaj.art-77a04ea34aa64aa087b00ffe0ff3c610 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-03-10T22:16:27Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-77a04ea34aa64aa087b00ffe0ff3c6102023-11-19T12:26:16ZengBMCMalaria Journal1475-28752023-10-0122111410.1186/s12936-023-04729-6Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian AmazonCamille Sena-dos-Santos0Giovanna C. Cavalcante1Diego Marques2Caio S. Silva3Milene Raiol de Moraes4Pablo Pinto5Mayara Natália Santana-da-Silva6Rafaella S. Ferraz7Sheyla Patrícia T. Costa8Ana Maria R. Ventura9Marinete M. Póvoa10Maristela G. Cunha11Ândrea Ribeiro-dos-Santos12Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA)Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA)Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA)Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA)Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA)Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA)Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA)Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA)Laboratory of Microbiology and Immunology, Federal University of Pará (UFPA)Division of Parasitology, Evandro Chagas Institute (IEC)Division of Parasitology, Evandro Chagas Institute (IEC)Laboratory of Microbiology and Immunology, Federal University of Pará (UFPA)Laboratory of Human and Medical Genetics, Program of Genetics and Molecular Biology, Federal University of Pará (UFPA)Abstract 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.https://doi.org/10.1186/s12936-023-04729-6MalariaPlasmodiumApoptosisGenetic ancestryGenetic markers |
| spellingShingle | Camille Sena-dos-Santos Giovanna C. Cavalcante Diego Marques Caio S. Silva Milene Raiol de Moraes Pablo Pinto Mayara Natália Santana-da-Silva Rafaella S. Ferraz Sheyla Patrícia T. Costa Ana Maria R. Ventura Marinete M. Póvoa Maristela G. Cunha Ândrea Ribeiro-dos-Santos Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian Amazon Malaria Journal Malaria Plasmodium Apoptosis Genetic ancestry Genetic markers |
| 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 | Malaria Plasmodium Apoptosis Genetic ancestry Genetic markers |
| url | https://doi.org/10.1186/s12936-023-04729-6 |
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