Association of IL-10 gene polymorphism with the susceptibility to dengue and disease severity in a population with asymptomatic and symptomatic dengue.

Abstract

Infections caused by Orthoflavivirus denguei can either manifest asymptomatically or present a wide spectrum of clinical manifestations. This variety of symptoms results from its complex pathogenesis, which is influenced by viral factors, in addition to host genetics and immunological factors. It is known that anti-inflammatory cytokines can play an immunomodulatory role throughout the course of dengue. Therefore, we investigated the single nucleotide polymorphisms (SNPs) -1082 A/G (rs1800896) and -819 C/T (rs1800871) in the interleukin-10 (IL-10) gene and their possible relationship with the development of symptomatic dengue in a Brazilian population. This study, carried out in northeastern Brazil, involved 333 volunteers, including 74 patients with dengue without warning signs (DWWS), 45 patients with dengue with warning signs (DWAS), 85 patients with asymptomatic dengue infection (ASY) and 129 health controls. The genomic DNA was extracted and the SNPs were genotyped using quantitative real-time polymerase chain reaction (qPCR). The data obtained were used to conduct statistical analyses of the genotype and allele frequencies. We observed an association of A/G and G/G genotypes of the -1082 A/G SNP of the IL-10 gene with susceptibility to symptomatic dengue and DWAS regarding the asymptomatic dengue. The G allele of this SNP has also been identified as a risk factor for symptomatic dengue, DWWS and DWAS. Regarding the analyses between the SNPs -1082 A/G and -819 C/T of the IL-10 gene, there was an association of the G-C haplotype with symptomatic dengue, DWWS and DWAS, as well as a correlation of the A-C haplotype with asymptomatic dengue. Moreover, the data indicate an association between the presence of the G allele and the development of symptoms, compared to those without the G allele. Our results indicate the presence of the G allele of SNP -1082 A/G of the IL-10 gene as a risk factor for the clinical development of symptomatic dengue in the studied population and show the importance of genomics association studies involving asymptomatic individuals.