Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/51147 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. |
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Bezerra, Ohanna Cavalcanti de LimaAlvarado-Arnez, Lucia ElenaMabunda, NédioSalomé, GraçaSousa, Amina deKehd, Fernanda de Souza GomesMarques, Carolinne SalesManta, Fernanda Saloum de NevesAndrade, Rafaela MotaFerreira, Laís PereiraLeal-Calvo, ThyagoCardoso, Cynthia ChesterNunes, KellyGouveia, Mateus H.Mbulaiteve, Sam M.Yeboah, Edward D.Hsing, AnnLatini, Ana Carla PereiraLeturiondo, André LuizRodrigues, Fabíola da CostaNoronha, Ariani BatistaFerreira, Cynthia de OliveiraTalhari, CarolinaRêgo, Jamile LeãoCastellucci, Léa Cristina de CarvalhoSantos, Eduardo TarazonaCarvalho, Elizeu Fagundes deMeyer, DiogoPinheiro, Roberta OlmoJani, Ilesh V.Pacheco, Antonio GuilhermeMoraes, Milton Ozório2022-02-10T19:27:33Z2022-02-10T19:27:33Z2021BEZERRA. Ohanna Cavalcanti de Lima et al. Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations. PLoS Negl Trop Dis., v. 15, n. 8, e0009434, p. 1 - 26, Aug. 2021.1935-2727https://www.arca.fiocruz.br/handle/icict/5114710.1371/journal. pntd.0009434engPublic Library of SciencePolimorfismos selecionadosPatógenos putativosgene PKLRAssociados à suscetibilidade a micobactériasPopulações brasileiras e africanasPutative pathogenSelected polymorphismsgene PKLRAssociated with mycobacterial susceptibilityBrazlian populationsAfrican populationsPutative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populationsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / National Research Coordination, Franz Tamayo University (UNIFRAZ). Cochabamba, Bolivia.Laboratory of Molecular Virology, Instituto Nacional de Saúde. Maputo, Mozambique.Medical Faculty, Eduardo Mondlane University. Maputo, Mozambique.Laboratory of Molecular Virology, Instituto Nacional de Saúde. Maputo, Mozambique.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Universidade Federal de Alagoas. Laboratório de Genética e Biologia Celular. Arapiraca, AL, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Departamento de Genética. Laboratórioo de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade de São Paulo. Instituto de Biociências. Laboratório de Genética Evolutiva e Biologia. São Paulo, SP, Brasil.Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health. Bethesda, Maryland, USA.Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health. Bethesda, Maryland, USA.University of Ghana Medical School. Accra, Ghana.Stanford Cancer Institute, Stanford University. Stanford, California, USA.Instituto Lauro de Souza Lima. Setor de Farmacologia. Bauru, SP, Brasil.Fundação Alfredo da Matta. Laboratório de Biologia Molecular. Manaus, AM. Brasil.Fundação Alfredo da Matta. Laboratório de Biologia Molecular. Manaus, AM. Brasil.Fundação Alfredo da Matta. Laboratório de Biologia Molecular. Manaus, AM. Brasil.Fundação Alfredo da Matta. Laboratório de Biologia Molecular. Manaus, AM. Brasil.Fundação Alfredo da Matta. Laboratório de Biologia Molecular. Manaus, AM. Brasil.Universidade Federal do Bahia. Hospital Universitário. Professor Edgard Santos. Serviço de Imunologia. Salvador, BA , Brasil .Universidade Federal do Bahia. Hospital Universitário. Professor Edgard Santos. Serviço de Imunologia. Salvador, BA , Brasil .Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia. Belo Horizonte, MG, Brasil.Universidade do Estado do Rio de Janeiro. Laboratório de Diagnóstico de DNA. Rio de Janeiro, RJ, Brasil.Universidade de São Paulo. Instituto de Biociências. Laboratório de Genética Evolutiva e Biologia. São Paulo, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Laboratory of Molecular Virology, Instituto Nacional de Saúde. Maputo, Mozambique.Fundação Oswaldo Cruz. Programa de Computação Científica - (PROCC). Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Pyruvate kinase (PK), encoded by the PKLR gene, is a key player in glycolysis controlling the integrity of erythrocytes. Due to Plasmodium selection, mutations for PK deficiency, which leads to hemolytic anemia, are associated with resistance to malaria in sub-Saharan Africa and with susceptibility to intracellular pathogens in experimental models. In this casecontrol study, we enrolled 4,555 individuals and investigated whether PKLR single nucleotide polymorphisms (SNPs) putatively selected for malaria resistance are associated with susceptibility to leprosy across Brazil (Manaus–North; Salvador–Northeast; Rondono´ polis– Midwest and Rio de Janeiro–Southeast) and with tuberculosis in Mozambique. Haplotype T/ G/G (rs1052176/rs4971072/rs11264359) was associated with leprosy susceptibility in Rio de Janeiro (OR = 2.46, p = 0.00001) and Salvador (OR = 1.57, p = 0.04), and with tuberculosis in Mozambique (OR = 1.52, p = 0.07). This haplotype downregulates PKLR expression in nerve and skin, accordingly to GTEx, and might subtly modulate ferritin and haptoglobin levels in serum. Furthermore, we observed genetic signatures of positive selection in the HCN3 gene (xpEHH>2 –recent selection) in Europe but not in Africa, involving 6 SNPs which are PKLR/HCN3 eQTLs. However, this evidence was not corroborated by the other tests (FST, Tajima’s D and iHS). Altogether, we provide evidence that a common PKLR locus in Africans contribute to mycobacterial susceptibility in African descent populations and also highlight, for first, PKLR as a susceptibility gene for leprosy and TB.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/51147/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALOhanaBezerra_Fernandamanta_ChesterCardoso_etal_IOC_2021.pdfOhanaBezerra_Fernandamanta_ChesterCardoso_etal_IOC_2021.pdfapplication/pdf1841516https://www.arca.fiocruz.br/bitstream/icict/51147/2/OhanaBezerra_Fernandamanta_ChesterCardoso_etal_IOC_2021.pdf3137b9e2dd29ac6a6e6ceb93a9ffa0dcMD52icict/511472022-02-10 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| dc.title.pt_BR.fl_str_mv |
Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations |
| title |
Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations |
| spellingShingle |
Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations Bezerra, Ohanna Cavalcanti de Lima Polimorfismos selecionados Patógenos putativos gene PKLR Associados à suscetibilidade a micobactérias Populações brasileiras e africanas Putative pathogen Selected polymorphisms gene PKLR Associated with mycobacterial susceptibility Brazlian populations African populations |
| title_short |
Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations |
| title_full |
Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations |
| title_fullStr |
Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations |
| title_full_unstemmed |
Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations |
| title_sort |
Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations |
| author |
Bezerra, Ohanna Cavalcanti de Lima |
| author_facet |
Bezerra, Ohanna Cavalcanti de Lima Alvarado-Arnez, Lucia Elena Mabunda, Nédio Salomé, Graça Sousa, Amina de Kehd, Fernanda de Souza Gomes Marques, Carolinne Sales Manta, Fernanda Saloum de Neves Andrade, Rafaela Mota Ferreira, Laís Pereira Leal-Calvo, Thyago Cardoso, Cynthia Chester Nunes, Kelly Gouveia, Mateus H. Mbulaiteve, Sam M. Yeboah, Edward D. Hsing, Ann Latini, Ana Carla Pereira Leturiondo, André Luiz Rodrigues, Fabíola da Costa Noronha, Ariani Batista Ferreira, Cynthia de Oliveira Talhari, Carolina Rêgo, Jamile Leão Castellucci, Léa Cristina de Carvalho Santos, Eduardo Tarazona Carvalho, Elizeu Fagundes de Meyer, Diogo Pinheiro, Roberta Olmo Jani, Ilesh V. Pacheco, Antonio Guilherme Moraes, Milton Ozório |
| author_role |
author |
| author2 |
Alvarado-Arnez, Lucia Elena Mabunda, Nédio Salomé, Graça Sousa, Amina de Kehd, Fernanda de Souza Gomes Marques, Carolinne Sales Manta, Fernanda Saloum de Neves Andrade, Rafaela Mota Ferreira, Laís Pereira Leal-Calvo, Thyago Cardoso, Cynthia Chester Nunes, Kelly Gouveia, Mateus H. Mbulaiteve, Sam M. Yeboah, Edward D. Hsing, Ann Latini, Ana Carla Pereira Leturiondo, André Luiz Rodrigues, Fabíola da Costa Noronha, Ariani Batista Ferreira, Cynthia de Oliveira Talhari, Carolina Rêgo, Jamile Leão Castellucci, Léa Cristina de Carvalho Santos, Eduardo Tarazona Carvalho, Elizeu Fagundes de Meyer, Diogo Pinheiro, Roberta Olmo Jani, Ilesh V. Pacheco, Antonio Guilherme Moraes, Milton Ozório |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Bezerra, Ohanna Cavalcanti de Lima Alvarado-Arnez, Lucia Elena Mabunda, Nédio Salomé, Graça Sousa, Amina de Kehd, Fernanda de Souza Gomes Marques, Carolinne Sales Manta, Fernanda Saloum de Neves Andrade, Rafaela Mota Ferreira, Laís Pereira Leal-Calvo, Thyago Cardoso, Cynthia Chester Nunes, Kelly Gouveia, Mateus H. Mbulaiteve, Sam M. Yeboah, Edward D. Hsing, Ann Latini, Ana Carla Pereira Leturiondo, André Luiz Rodrigues, Fabíola da Costa Noronha, Ariani Batista Ferreira, Cynthia de Oliveira Talhari, Carolina Rêgo, Jamile Leão Castellucci, Léa Cristina de Carvalho Santos, Eduardo Tarazona Carvalho, Elizeu Fagundes de Meyer, Diogo Pinheiro, Roberta Olmo Jani, Ilesh V. Pacheco, Antonio Guilherme Moraes, Milton Ozório |
| dc.subject.other.pt_BR.fl_str_mv |
Polimorfismos selecionados Patógenos putativos gene PKLR Associados à suscetibilidade a micobactérias Populações brasileiras e africanas |
| topic |
Polimorfismos selecionados Patógenos putativos gene PKLR Associados à suscetibilidade a micobactérias Populações brasileiras e africanas Putative pathogen Selected polymorphisms gene PKLR Associated with mycobacterial susceptibility Brazlian populations African populations |
| dc.subject.en.pt_BR.fl_str_mv |
Putative pathogen Selected polymorphisms gene PKLR Associated with mycobacterial susceptibility Brazlian populations African populations |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. |
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2021 |
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2021 |
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2022-02-10T19:27:33Z |
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2022-02-10T19:27:33Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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BEZERRA. Ohanna Cavalcanti de Lima et al. Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations. PLoS Negl Trop Dis., v. 15, n. 8, e0009434, p. 1 - 26, Aug. 2021. |
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https://www.arca.fiocruz.br/handle/icict/51147 |
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1935-2727 |
| dc.identifier.doi.none.fl_str_mv |
10.1371/journal. pntd.0009434 |
| identifier_str_mv |
BEZERRA. Ohanna Cavalcanti de Lima et al. Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations. PLoS Negl Trop Dis., v. 15, n. 8, e0009434, p. 1 - 26, Aug. 2021. 1935-2727 10.1371/journal. pntd.0009434 |
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Public Library of Science |
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