Abstract
Dengue manifestations range from a mild form, dengue fever (DF), to more severe forms such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The ability of the host to present one of these clinical forms could be related to polymorphisms located in genes of the Toll-like receptors (TLRs) which activate the pro-inflammatory response. Therefore, the genotyping of single nucleotide genetic polymorphisms (SNPs) in TLR3 (rs3775291 and rs6552950), TLR4 (rs2737190, rs10759932, rs4986790, rs4986791, rs11536865, and rs10983755), TLR7 (rs179008 and rs3853839), and TLR8 (rs3764880, rs5741883, rs4830805, and rs1548731) was carried out in non-genetically related DHF patients, DF patients, and general population (GP) subjects. The SNPs were analyzed by real-time PCR by genotyping assays from Applied Biosystems®. The codominance model showed that dengue patients had a lower probability of presenting the TLR4-rs2737190-G/G genotype (odds ratio (OR) (95% CI) = 0.34 (0.14–0.8), p = 0.038). Dengue patients showed a lower probability of presenting TLR4-rs11536865-G/C genotype (OR (95% CI) = 0.19 (0.05–0.73), p = 0.0092) and had a high probability of presenting the TACG haplotype, but lower probability of presenting the TGCG haplotype in the TLR4 compared to GP individuals (OR (95% CI) = 0.55 (0.35–0.86), p = 0.0084). In conclusion, the TLR4-rs2737190-G/G and TLR4-rs11536865-G/C genotypes and TGCG haplotype were associated with protection from dengue.
Highlights
Dengue fever is a disease caused by the dengue virus, a positive sense single-stranded RNA virus, which has four serotypes, DENV-1, DENV-2, DENV-3, and DENV-4 [1]
The most relevant factors are the immunological status and polymorphisms in genes related to the immune response [4]
We analyzed the immunological status of dengue patients and found that IgG1 increased significantly in the sera of dengue hemorrhagic fever (DHF) patients with secondary infections
Summary
Dengue fever is a disease caused by the dengue virus, a positive sense single-stranded RNA virus, which has four serotypes, DENV-1, DENV-2, DENV-3, and DENV-4 [1]. Dengue hemorrhagic fever has been associated with infections by the serotype DENV-2 due to its genetic variation, replication efficiency, and genotype. The disease may be aggravated by the presence of pre-existing heterotypic antibodies; when the virus-antibody complexes bind to the. Fc receptors, they facilitate the infection of target cells, causing an increase in viraemia and cytokine levels [2]. It has been documented that single nucleotide genetic polymorphisms (SNPs) in cytokines (TNF-308, TGFβ1-509) and receptors (DC-SIGN-336) are associated with susceptibility to DHF [3,4,5]
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