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https://www.arca.fiocruz.br/handle/icict/62358
A MULTI-CENTER, PROSPECTIVE COHORT STUDY OF WHOLE BLOOD GENE EXPRESSION IN THE TUBERCULOSIS-DIABETES INTERACTION
Tuberculose
Expressão genetica
Brasil e Índia
Sequenciamento de RNA
Resistência a insulina
Tuberculosis
Gene expression
Brazil and India
RNA sequencing
Insulin resistance
Author
Queiroz, Artur T. L.
Vinhaes, Caian L.
Fukutani, Eduardo R.
Gupte, Akshay N.
Kumar, Nathella Pavan
Fukutani, Kiyoshi F.
Arriaga, María B.
Sterling, Timothy R.
Babu, Subash
Gaikwad, Sanjay
Karyakarte, Rajesh
Mave, Vidya
Paradhkar, Mandar
Viswanathan, Vijay
Gupta, Amita
Andrade, Bruno B.
Kornfeld, Hardy
Vinhaes, Caian L.
Fukutani, Eduardo R.
Gupte, Akshay N.
Kumar, Nathella Pavan
Fukutani, Kiyoshi F.
Arriaga, María B.
Sterling, Timothy R.
Babu, Subash
Gaikwad, Sanjay
Karyakarte, Rajesh
Mave, Vidya
Paradhkar, Mandar
Viswanathan, Vijay
Gupta, Amita
Andrade, Bruno B.
Kornfeld, Hardy
Affilliation
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil.
Johns Hopkins Bloomberg School of Public Health. Baltimore, MD, USA.
National Institutes of Health‐ NIRT ‐ International Center for Excellence in Research, Chennai, India.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil.
Division of Infectious Diseases, Department of Medicine. Vanderbilt University Medical Center. Nashville, TN, USA.
National Institutes of Health‐ NIRT ‐ International Center for Excellence in Research, Chennai, India.
Department of Pulmonary Medicine. Byramjee-Jeejeebhoy Government Medical College and Sassoon General Hospitals. Pune, India.
Department of Microbiology. Byramjee-Jeejeebhoy Government Medical College and Sassoon General Hospitals. Pune, India.
Byramjee-Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site. Pune, India / Johns Hopkins Center for Infectious Diseases in India. Pune, India.
Byramjee-Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site. Pune, India / Johns Hopkins Center for Infectious Diseases in India. Pune, India.
Prof. M. Viswanathan Diabetes Research Centre. Chennai, India.
Johns Hopkins Bloomberg School of Public Health. Baltimore, MD, USA.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil. / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Instituto de Pesquisa Clínica e Translacional. Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA / UMass Chan Medical School. Worcester, MA, USA.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Centro de Integração de Dados e Conhecimentos para Saúde. Salvador, BA, Brasil.
Johns Hopkins Bloomberg School of Public Health. Baltimore, MD, USA.
National Institutes of Health‐ NIRT ‐ International Center for Excellence in Research, Chennai, India.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil.
Division of Infectious Diseases, Department of Medicine. Vanderbilt University Medical Center. Nashville, TN, USA.
National Institutes of Health‐ NIRT ‐ International Center for Excellence in Research, Chennai, India.
Department of Pulmonary Medicine. Byramjee-Jeejeebhoy Government Medical College and Sassoon General Hospitals. Pune, India.
Department of Microbiology. Byramjee-Jeejeebhoy Government Medical College and Sassoon General Hospitals. Pune, India.
Byramjee-Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site. Pune, India / Johns Hopkins Center for Infectious Diseases in India. Pune, India.
Byramjee-Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site. Pune, India / Johns Hopkins Center for Infectious Diseases in India. Pune, India.
Prof. M. Viswanathan Diabetes Research Centre. Chennai, India.
Johns Hopkins Bloomberg School of Public Health. Baltimore, MD, USA.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil. / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Instituto de Pesquisa Clínica e Translacional. Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA / UMass Chan Medical School. Worcester, MA, USA.
Abstract
Diabetes mellitus (DM) increases tuberculosis (TB) severity. We compared blood gene expression in adults with pulmonary TB, with or without diabetes mellitus (DM) from sites in Brazil and India. RNA sequencing (RNAseq) performed at baseline and during TB treatment. Publicly available baseline RNAseq data from South Africa and Romania reported by the TANDEM Consortium were also analyzed. Across the sites, differentially expressed genes varied for each condition (DM, TB, and TBDM) and no pattern classified any one group across all sites. A concise signature of TB disease was identified but this was expressed equally in TB and TBDM. Pathway enrichment analysis failed to distinguish TB from TBDM, although there was a trend for greater neutrophil and innate immune pathway activation in TBDM participants. Pathways associated with insulin resistance, metabolic dysfunction, diabetic complications, and chromosomal instability were positively correlated with glycohemoglobin. The immune response to pulmonary TB as reflected by whole blood gene expression is substantially similar with or without comorbid DM. Gene expression pathways associated with the microvascular and macrovascular complications of DM are upregulated during TB, supporting a syndemic interaction between these coprevalent diseases.
Keywords in Portuguese
Diabetes mellitusTuberculose
Expressão genetica
Brasil e Índia
Sequenciamento de RNA
Resistência a insulina
Keywords
Diabetes mellitusTuberculosis
Gene expression
Brazil and India
RNA sequencing
Insulin resistance
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