Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.7/373
Título: NOS2 Variants Reveal a Dual Genetic Control of Nitric Oxide Levels, Susceptibility to Plasmodium Infection, and Cerebral Malaria
Autor: Trovoada, M. d. J.
Martins, M.
Ben Mansour, R.
Sambo, M. d. R.
Fernandes, A. B.
Antunes Goncalves, L.
Borja, A.
Moya, R.
Almeida, P.
Costa, J.
Marques, I.
Macedo, M. P.
Coutinho, A.
Narum, D. L.
Penha-Goncalves, C.
Palavras-chave: Malaria
Plasmodium Infection
Nitric Oxide
Data: 2013
Editora: American Society for Microbiology
Citação: Host Response and Inflammation: NOS2 Variants Reveal a Dual Genetic Control of Nitric Oxide Levels, Susceptibility to Plasmodium Infection, and Cerebral Malaria, Maria de Jesus Trovoada, Madalena Martins, Riadh Ben Mansour, Maria do Rosário Sambo, Ana B. Fernandes, Lígia Antunes Gonçalves, Artur Borja, Roni Moya, Paulo Almeida, João Costa, Isabel Marques, M. Paula Macedo, António Coutinho, David L. Narum, and Carlos Penha-Gonçalves Infect. Immun. March 2014 82:3 1287-1295; Accepted manuscript posted online 30 December 2013, doi:10.1128/IAI.01070-13
Resumo: Nitric oxide (NO) is a proposed component of malaria pathogenesis, and the inducible nitric oxide synthase gene (NOS2) has been associated to malaria susceptibility. We analyzed the role of NOS2 polymorphisms on NO bioavailability and on susceptibility to infection, Plasmodium carrier status and clinical malaria. Two distinct West African sample collections were studied: a population-based collection of 1,168 apparently healthy individuals from the Príncipe Island and a hospital-based cohort of 269 Angolan children. We found that two NOS2 promoter single-nucleotide polymorphism (SNP) alleles associated to low NO plasma levels in noninfected individuals were also associated to reduced risk of pre-erythrocytic infection as measured anti-CSP antibody levels (6.25E-04 < P < 7.57E-04). In contrast, three SNP alleles within the NOS2 cistronic region conferring increased NO plasma levels in asymptomatic carriers were strongly associated to risk of parasite carriage (8.00E-05 < P < 7.90E-04). Notwithstanding, three SNP alleles in this region protected from cerebral malaria (7.90E-4 < P < 4.33E-02). Cohesively, the results revealed a dual regimen in the genetic control of NO bioavailability afforded by NOS2 depending on the infection status. NOS2 promoter variants operate in noninfected individuals to decrease both NO bioavailability and susceptibility to pre-erythrocytic infection. Conversely, NOS2 cistronic variants (namely, rs6505469) operate in infected individuals to increase NO bioavailability and confer increased susceptibility to unapparent infection but protect from cerebral malaria. These findings corroborate the hypothesis that NO anti-inflammatory properties impact on different steps of malaria pathogenesis, explicitly by favoring infection susceptibility and deterring severe malaria syndromes.
Peer review: yes
URI: http://hdl.handle.net/10400.7/373
DOI: 10.1128/IAI.01070-13
Versão do Editor: http://iai.asm.org/content/82/3/1287.long
Aparece nas colecções:IR - Publications
DG - Artigos em revistas científicas
BCBU- Artigos

Ficheiros deste registo:
Ficheiro Descrição TamanhoFormato 
Infect. Immun.-2014-Trovoada-1287-95.pdfartigo principal669,5 kBAdobe PDFVer/Abrir


FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpace
Formato BibTex MendeleyEndnote Degois 

Todos os registos no repositório estão protegidos por leis de copyright, com todos os direitos reservados.