| Author | Bezerra, Ohanna Cavalcanti de Lima | |
| Author | Alvarado Arnez, Lucia Elena | |
| Author | Mabunda, Nédio | |
| Author | Salomé, Graça | |
| Author | Sousa, Amina de | |
| Author | Kehdy, Fernanda de Souza Gomes | |
| Author | Marques, Carolinne de Sales | |
| Author | Manta, Fernanda Saloum de Neves | |
| Author | Andrade, Rafaela Mota | |
| Author | Bento, Laís Pereira Ferreira | |
| Author | Calvo, Thyago Leal | |
| Author | Cardoso, Cynthia Chester | |
| Author | Nunes, Kelly | |
| Author | Gouveia, Mateus Henrique | |
| Author | Mbulaiteve, Sam M. | |
| Author | Yeboah, Edward D. | |
| Author | Hsing, Ann | |
| Author | Latini, Ana Carla Pereira | |
| Author | Leturiondo, André Luiz | |
| Author | Rodrigues, Fabíola da Costa | |
| Author | Noronha, Ariani Batista | |
| Author | Ferreira, Cynthia de Oliveira | |
| Author | Cortez, Carolina Chrusciak Talhari | |
| Author | Rêgo, Jamile Leão | |
| Author | Castellucci, Léa Cristina de Carvalho | |
| Author | Tarazona Santos, Eduardo Martín | |
| Author | Carvalho, Elizeu Fagundes de | |
| Author | Meyer, Diogo | |
| Author | Pinheiro, Roberta Olmo | |
| Author | Jani, Ilesh V. | |
| Author | Pacheco, Antonio Guilherme Fonseca | |
| Author | Moraes, Milton Ozório | |
| Access date | 2022-02-10T19:27:33Z | |
| Available date | 2022-02-10T19:27:33Z | |
| Document date | 2021 | |
| Citation | 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 Neglected Tropical Diseases, v. 15, n. 8, p. 1-26, 27 Aug. 2021. | |
| ISSN | 1935-2727 | |
| URI | https://www.arca.fiocruz.br/handle/icict/51147 | |
| Description | Produção científica do Laboratório de Hanseníase. | pt_BR |
| Sponsorship | This study was financed by the Brazilian National Council for Scientific and Technological Development (CNPq; Milton Ozório Moraes - 421852/2017-2018; Antonio Guilherme Fonseca Pacheco - 307489/2018-3). | |
| Sponsorship | Foundation for Research Support of the State of Rio de Janeiro (FAPERJ; Milton Ozório Moraes - E-26/203.053/2016; AGP - E-26/203.172/2017). | |
| Sponsorship | National Fund for Health/Brazilian Ministry of Health (MS/SCTIE/DECIT; Milton Ozório Moraes - 404277/2012-8). | |
| Language | eng | en_US |
| Publisher | Public Library of Science | |
| Rights | open access | |
| Title | Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in brazilian and african populations | en_US |
| Type | Article | |
| DOI | 10.1371/journal. pntd.0009434 | |
| Abstract | 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 case-control 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; Rondonópolis–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. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Franz Tamayo University. National Research Coordination. Cochabamba, Bolivia. | |
| Affilliation | Instituto Nacional de Saúde. Laboratory of Molecular Virology. Maputo, Mozambique. | |
| Affilliation | Eduardo Mondlane University. Medical Faculty. Maputo, Mozambique. | |
| Affilliation | Instituto Nacional de Saúde. Laboratory of Molecular Virology. Maputo, Mozambique. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | 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. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biologia. Departamento de Genética. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade de São Paulo. Instituto de Biociências. Laboratório de Genética Evolutiva e Biologia. São Paulo, SP, Brasil. | |
| Affilliation | National Institutes of Health. National Human Genome Research Institute. Center for Research on Genomics and Global Health. Bethesda, MD, USA. | |
| Affilliation | National Institutes of Health. National Human Genome Research Institute. Center for Research on Genomics and Global Health. Bethesda, MD, USA. | |
| Affilliation | University of Ghana Medical School. Accra, Ghana. | |
| Affilliation | Stanford University. Stanford Cancer Institute. Stanford, CA, USA. | |
| Affilliation | Instituto Lauro de Souza Lima. Setor de Farmacologia. Bauru, SP, Brasil. | |
| Affilliation | Fundação Alfredo da Matta. Laboratório de Biologia Molecular. Manaus, AM, Brasil. | |
| Affilliation | Fundação Alfredo da Matta. Laboratório de Biologia Molecular. Manaus, AM, Brasil. | |
| Affilliation | Fundação Alfredo da Matta. Laboratório de Biologia Molecular. Manaus, AM, Brasil. | |
| Affilliation | Fundação Alfredo da Matta. Laboratório de Biologia Molecular. Manaus, AM, Brasil. | |
| Affilliation | Fundação Alfredo da Matta. Laboratório de Biologia Molecular. Manaus, AM, Brasil. | |
| Affilliation | Universidade Federal do Bahia. Hospital Universitário. Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil. | |
| Affilliation | Universidade Federal do Bahia. Hospital Universitário. Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil. | |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia. Belo Horizonte, MG, Brasil. | |
| Affilliation | Universidade do Estado do Rio de Janeiro. Centro Biomédico. Instituto de Biologia Roberto Alcantara Gomes. Laboratório de Diagnóstico de DNA. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade de São Paulo. Instituto de Biociências. Laboratório de Genética Evolutiva e Biologia. São Paulo, SP, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Instituto Nacional de Saúde. Laboratory of Molecular Virology. Maputo, Mozambique. | |
| Affilliation | Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Subject | Single nucleotide polymorphisms | en_US |
| Subject | Haplotypes | en_US |
| Subject | Brazil | en_US |
| Subject | Leprosy | en_US |
| Subject | Genomics | en_US |
| Subject | Europe | en_US |
| Subject | Malaria | en_US |
| Subject | Mycobacterium tuberculosis | en_US |
| e-ISSN | 1935-2735 | |
