Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects

dc.creatorCarvalho, Caroline Xavier
dc.creatorCezar, Renata Duarte da Silva
dc.creatorFreire, Naishe Matos
dc.creatorVasconcelos, Carla Maria Mola de
dc.creatorSolorzano, Victor Edgar Fiestas
dc.creatorPinto, Thiago Gomes de Toledo
dc.creatorFialho, Luciana Gomes
dc.creatorCarmo, Rodrigo Feliciano do
dc.creatorVasconcelos, Luydson Richardson Silva
dc.creatorCordeiro, Marli Tenório
dc.creatorBaptista, Paulo
dc.creatorAzeredo, Elzinandes Leal de
dc.creatorCunha, Rivaldo Venâncio da
dc.creatorSouza, Luiz José de
dc.creatorPacheco, Antonio Guilherme
dc.creatorKubelka, Claire Fernandes
dc.creatorMoura, Patrícia Muniz Mendes Freire de
dc.creatorMoraes, Milton Ozório
dc.date2017-10-17T15:40:47Z
dc.date2017-10-17T15:40:47Z
dc.date2017
dc.date.accessioned2023-09-26T23:21:00Z
dc.date.available2023-09-26T23:21:00Z
dc.identifierCARVALHO, Caroline Xavier et al. Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects. Human Immunology, p. 1-8, 2017.
dc.identifier0198-8859
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/22847
dc.identifier10.1016/j.humimm.2017.07.013
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8889606
dc.descriptionOutbreaks of the Zika, dengue, and chikungunya viruses, especially in the Americas, pose a global threat due to their rapid spread and difficulty controlling the vector. Extreme phenotypes are often observed, from asymptomatic to severe clinical manifestations, which are well-studied in dengue. Host variations are also important contributors to disease outcomes, and many case-control studies have associated single nucleotide polymorphisms (SNPs) with severe dengue. Here, we found that the TC genotype and T-carriers for SNP rs1285933 in the C-type lectin superfamily member 5 (CLEC5A) gene was associated with severe dengue in a Northern Brazilian population (OR=2.75 and p-value=0.01, OR=2.11 and p-value=0.04, respectively). We also tested the functional effect of the CLEC5A protein and found that it is upregulated on the surface of human monocytes after in vitro dengue infection. CLEC5A was correlated with viral load inside the monocytes (Spearman r=0.55, p=0.008) and TNF production in culture supernatants (Spearman r=0.72, p=0.03). Analysis of mRNA in blood samples from DENV4-infected patients exhibiting mild symptoms showed that CLEC5A mRNA expression is correlated with TNF (r=0.67, p=0.0001) and other immune mediators. Monocytes from rs1285933 TT/TC individuals showed lower CLEC5A expression compared to CC genotypes. However, in these cells, CLEC5A was not correlated with TNF production. In summary, we confirmed that CLEC5A is genetically associated with dengue severity outcome, playing a central role during the immune response triggered by a dengue viral infection, and rs1285933 is a relevant SNP that is able to regulate signaling pathways after interactions between the dengue virus and CLEC5A receptors.
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsopen access
dc.subjectDengue
dc.subjectPolimorfismo
dc.subjectFator de Necrose Tumoral
dc.subjectDengue
dc.subjectCLEC5A
dc.subjectPolymorphisms
dc.subjectSevere dengue
dc.subjectSNPs
dc.subjectTNF
dc.titleAssociation of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects
dc.typeArticle


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