Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7939
Title: Association between the haptoglobin and heme oxygenase 1 genetic profiles and soluble CD163 in susceptibility to and severity of human malaria
Authors: Mendonça, Vitor Rosa Ramos de
Luz, Nívea Farias
Santos, Nadja de Jesus Gonçalves dos
Borges, Valeria de Matos
Gonçalves, Marilda de Souza
Andrade, Bruno de Bezerril
Barral Netto, Manoel
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). São Paulo, SP, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil
National Institute of Allergy and Infectious Diseases. National Institutes of Health. Immunobiology Section. Laboratory of Parasitic Diseases. Bethesda, Maryland, USAe
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). São Paulo, SP, Brasil
Abstract: Intravascular hemolysis is a hallmark event in the immunopathology of malaria that results in increased systemic concentrations of free hemoglobin (Hb). The oxidation of Hb by free radicals causes the release of heme, which amplifies inflammation. To circumvent the detrimental effects of free heme, hosts have developed several homeostatic mechanisms, including the enzyme haptoglobin (Hp), which scavenges cell-free Hb, the monocyte receptor CD163, which binds to Hb-Hp complexes, and heme oxygenase-1 (HO-1), which degrades intracellular free heme. We tested the association between these three main components of the host response to hemolysis and susceptibility to malaria in a Brazilian population. The genetic profiles of the HMOX1 and Hp genes and the plasma levels of a serum inflammatory marker, the soluble form of the CD163 receptor (sCD163), were studied in 264 subjects, including 78 individuals with symptomatic malaria, 106 individuals with asymptomatic malaria, and 80 uninfected individuals. We found that long (GT)n repeats in the microsatellite polymorphism region of the HMOX1 gene, the Hp2 allele, and the Hp2.2 genotype were associated with symptomatic malaria. Moreover, increased plasma concentrations of heme, Hp, HO-1, and sCD163 were associated with susceptibility to malaria. The validation of these results could support the development of targeted therapies and aid in reducing the severity of malaria
DeCS: Antígenos CD/sangue
Antígenos de Diferenciação Mielomonocítica/sangue
Haptoglobinas/genética
Heme Oxigenase-1/genética
Malária/genética
Malária/imunologia
Receptores de Superfície Celular/sangue
Adulto
Alelos
Brasil
Suscetibilidade a Doenças
Feminino
Haptoglobinas/metabolismo
Heme/metabolismo
Heme Oxigenase-1/metabolismo
Hemoglobinas/metabolismo
Humanos
Masculino
Repetições de Microssatélites
Meia-Idade
Polimorfismo Genético
Issue Date: 2012
Publisher: American Society for Microbiology
Citation: MENDONÇA, V. R. R. et al. Association between the haptoglobin and heme oxygenase 1 genetic profiles and soluble CD163 in susceptibility to and severity of human malaria. Infection and Immunity, v. 80, n. 4, p. 1445-1154, 2012.
DOI: 10.1128/IAI.05933-11
ISSN: 1098-5522
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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