dc.contributor |
Malheiro, Adriana |
dc.contributor.author |
Costa, Allyson Guimarães |
dc.contributor.author |
Ramasawmy, Rajendranath |
dc.contributor.author |
Hiochelson, Najibe |
dc.contributor.author |
Ibiapina, Santos |
dc.contributor.author |
Sampaio, Vanderson Souza |
dc.contributor.author |
Xabregas, Lilyane Amorim |
dc.contributor.author |
Brasil, Larissa Wanderley |
dc.contributor.author |
Tarrago, Andréa Monteiro |
dc.contributor.author |
Almeida, Anne Cristine Gomes |
dc.contributor.author |
Kuehn, Andrea |
dc.contributor.author |
Vitor Silva, Sheila |
dc.contributor.author |
Melo, Gisely Cardoso de |
dc.contributor.author |
Siqueira, André Machado |
dc.contributor.author |
Monteiro, Wuelton Marcelo |
dc.contributor.author |
Lacerda, Marcus Vinícius Guimarães |
dc.date |
2017-09-19T09:22:43Z |
dc.date |
2017-09-19T09:22:43Z |
dc.date |
2017-08-29 |
dc.date |
2017-09-06T18:00:26Z |
dc.identifier.citation |
1932-6203 |
dc.identifier.uri |
http://hdl.handle.net/2445/115595 |
dc.format |
14 p. |
dc.format |
application/pdf |
dc.language.iso |
eng |
dc.publisher |
Public Library of Science |
dc.relation |
Reproducció del document publicat a:
http://dx.doi.org/10.1371/journal.pone.0183840 |
dc.relation |
PloS one, 2017, vol. 12, num. 8, p. e0183840 |
dc.relation |
http://dx.doi.org/10.1371/journal.pone.0183840 |
dc.rights |
cc by (c) Costa et al., 2017 |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.rights |
http://creativecommons.org/licenses/by/4.0/ |
dc.subject |
Malària |
dc.subject |
Plasmodium vivax |
dc.subject |
Amazònia |
dc.subject |
Brasil |
dc.subject |
Malaria |
dc.subject |
Plasmodium vivax |
dc.subject |
Amazon River Region |
dc.subject |
Brazil |
dc.title |
Association of TLR variants with susceptibility to Plasmodium
vivax malaria and parasitemia in the Amazon region of Brazil |
dc.type |
info:eu-repo/semantics/article |
dc.type |
info:eu-repo/semantics/publishedVersion |
dc.description.abstract |
BACKGROUND: Plasmodium vivax malaria (Pv-malaria) is still
considered a neglected disease despite an alarming number of
individuals being infected annually. Malaria pathogenesis occurs
with the onset of the vector-parasite-host interaction through
the binding of pathogen-associated molecular patterns (PAMPs)
and receptors of innate immunity, such as toll-like receptors
(TLRs). The triggering of the signaling cascade produces an
elevated inflammatory response. Genetic polymorphisms in TLRs
are involved in susceptibility or resistance to infection, and
the identification of genes involved with Pv-malaria response is
important to elucidate the pathogenesis of the disease and may
contribute to the formulation of control and elimination tools.
METHODOLOGY/PRINCIPAL FINDINGS: A retrospective case-control
study was conducted in an intense transmission area of
Pv-malaria in the state of Amazonas, Brazil. Genetic
polymorphisms (SNPs) in different TLRs, TIRAP, and CD14 were
genotyped by polymerase chain reaction-restriction fragment
length polymorphism (PCR-RFLP) analysis in 325 patients infected
with P. vivax and 274 healthy individuals without malaria
history in the prior 12 months from the same endemic area.
Parasite load was determined by qPCR. Simple and multiple
logistic/linear regressions were performed to investigate
association between the polymorphisms and the occurrence of
Pv-malaria and parasitemia. The C/T (TLR5 R392StopCodon) and T/T
(TLR9 -1486C/T) genotypes appear to be risk factors for
infection by P. vivax (TLR5: C/C vs. C/T [OR: 2.116, 95% CI:
1.054-4.452, p = 0.031]; TLR9: C/C vs. T/T [OR: 1.919, 95% CI:
1.159-3.177, p = 0.010]; respectively). Fever (COEF = 7599.46,
95% CI = 3063.80-12135.12, p = 0.001) and the C/C genotype of
TLR9 -1237C/T (COEF = 17006.63, 95% CI = 3472.83-30540.44, p =
0.014) were independently associated with increased parasitemia
in patients with Pv-malaria. CONCLUSIONS: Variants of TLRs may
predispose individuals to infection by P. vivax. The TLR5
R392StopCodon and TLR9 -1486C/T variants are associated with
susceptibility to Pv-malaria. Furthermore, the TLR9 variant
-1237C/C correlates with high parasitemia. |