Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/12572
Title: Single nucleotide polymorphisms in candidate genes and dengue severity in children: A case–control, functional and meta-analysis study
Authors: Carvalho, Caroline Xavier
Gibson, Gerusa
Brasil, Patrícia
Ferreira, Ralph X.
Santos, Reinaldo de Souza
Cruz, Oswaldo Gonçalves
Oliveira, Solange Artimos de
Carvalho, MarÍlia de Sá
Pacheco, Antonio G.
Kubelka, Claire F.
Moraes, Milton Ozório
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sérgio Arouca. Departamento de Endemias Samuel Pessoa. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas (IPEC). Rio de Janeiro, RJ, Brasil.
Universidade Federal Fluminense. Hospital Universitário Antonio Pedro. Departamento de Medicina Clínica. Disciplina de Doenças Infecciosas e Parasitárias. Niterói, RJ, Brasil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sérgio Arouca. Departamento de Endemias Samuel Pessoa. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Programa de Computação Científica (PROCC). Rio de Janeiro, RJ, Brasil.
Universidade Federal Fluminense. Hospital Universitário Antonio Pedro. Departamento de Medicina Clínica. Disciplina de Doenças Infecciosas e Parasitárias. Niterói, RJ, Brasil.
Fundação Oswaldo Cruz. Programa de Computação Científica (PROCC). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Programa de Computação Científica (PROCC). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Abstract: Dengue is an arthropod-borneemerging viral disease with highmorbidity andmortality risk in tropical countries like Brazil. Clinical manifestations are vast, ranging from asymptomatic to most severe forms of dengue such as shock. Previous data have shown that host genetics play a role in disease susceptibility and severity. Herein, we have tested the association of single nucleotide polymorphisms (SNPs) at TNF, IL10, MIF, DCSIGN, CLEC5A, NOD2, CCR5 and MRC1 as candidate genes using a matched case–control study design including 88 severe children cases of dengue patients and 335 healthy unrelated subjects that was also separated in IgG+ and IgG controls. We demonstrated that the TT genotype of CLEC5A SNP (rs1285933 C>T) is associated with dengue severity (OR = 2.25; p = 0.03) and that GG genotype of 336G>A DCSIGN (CD209) SNP is associated with protection to severe dengue (OR = 0.12; p = 0.04). Both comparisons were borderline significant when cases were compared with IgG+ controls subgroup. Nevertheless, genotype–phenotype correlation was also assessed using serum levels of TNF from infected patients at the onset of dengue fever, and CT/TT carriers in CLEC5A secreted higher levels of TNF than CC individuals in 5–7 days of infection. No significant difference was observed in TNF levels between genotypes GG versus AG/AA at DCSIGN promoter. Next, we performed ameta-analysis retrieving results fromthe literature for 336G>ADCSIGNand 308G>ATNFSNPs demonstrating that the consensus estimates of these SNPs indicated no association with dengue severity (when compared to Dengue fever) in the overall analysis. But, a subgroup analysis in the 336G>A DCSIGN, the G allele was associated with severe dengue susceptibility in Asians (ORallele = 2.77; p = 0.0001; ORcarriers = 2.99; p = 0.0001) and protection in Brazilians (ORallele=0.66; p=0.013). In summary, our results suggest that genetic variations at CLEC5A increase the risk and regulate TNF secretion in dengue severity among Brazilians. Also, combined data of the literature suggest population-specific effect of the 336 DCSIGN SNP more prominent in Asians and in a different direction than Brazilians.
Keywords: CLEC5A
DC-SIGN
TNF
Dengue
DHF
Cytokines
DeCS: Dengue
Citocinas
Fator de Necrose Tumoral
Issue Date: 2013
Publisher: Elsevier
Citation: CARVALHO, Caroline Xavier; et al. Single nucleotide polymorphisms in candidate genes and dengue severity in children: A case–control, functional and meta-analysis study. Infection, Genetics and Evolution, v.20, p.197–205, 2013.
DOI: 10.1016/j.meegid.2013.08.017
ISSN: 1567-1348
Copyright: restricted access
Appears in Collections:INI - Artigos de Periódicos
ENSP - Artigos de Periódicos
Presidência Fiocruz – Artigos de Periódicos
IOC - Artigos de Periódicos

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