Single nucleotide polymorphisms in candidate genes and dengue severity in children: A case–control, functional and meta-analysis study

dc.creatorCarvalho, Caroline Xavier
dc.creatorGibson, Gerusa
dc.creatorBrasil, Patrícia
dc.creatorFerreira, Ralph X.
dc.creatorSantos, Reinaldo de Souza
dc.creatorCruz, Oswaldo Gonçalves
dc.creatorOliveira, Solange Artimos de
dc.creatorCarvalho, MarÍlia de Sá
dc.creatorPacheco, Antonio G.
dc.creatorKubelka, Claire F.
dc.creatorMoraes, Milton Ozório
dc.date2016-01-21T11:14:41Z
dc.date2016-01-21T11:14:41Z
dc.date2013
dc.date.accessioned2023-09-26T22:54:19Z
dc.date.available2023-09-26T22:54:19Z
dc.identifierCARVALHO, 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.
dc.identifier1567-1348
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/12572
dc.identifier10.1016/j.meegid.2013.08.017
dc.identifier1567-7257
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8884587
dc.descriptionDengue 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectCLEC5A
dc.subjectDC-SIGN
dc.subjectTNF
dc.subjectDengue
dc.subjectDHF
dc.subjectCytokines
dc.subjectDengue
dc.subjectCitocinas
dc.subjectFator de Necrose Tumoral
dc.titleSingle nucleotide polymorphisms in candidate genes and dengue severity in children: A case–control, functional and meta-analysis study
dc.typeArticle


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