Associação dos SNP TNFalfa rs361525 e SNP IL-10 rs1800872 com susceptibilidade à dengue: estudo caso controle na região Centro-Oeste do Brasil.

Abstract

Arboviruses are a group of viral diseases transmitted by arthropods, such as the Aedes aegypti mosquito, which is a vector for dengue, Zika, and yellow fever. In Brazil, climatic conditions favor the spread of this vector, contributing to the high incidence of dengue in several regions. The dengue virus (DENV), belonging to the Flaviviridae family, has five serotypes, broadening the clinical spectrum of the disease. DENV infection can range from mild to severe forms, with an increased risk of complications and death. The innate immune system is responsible for the initial response to the virus, with emphasis on macrophages and dendritic cells, which produce pro-inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-α), and antiinflammatory cytokines, such as Interleukin 10 (IL-10). TNF-α acts to regulate the immune response, promoting vasodilation and leukocyte recruitment, while IL-10 modulates excessive inflammation, balancing the antiviral response and reducing tissue damage. Population genomics studies have shown that single nucleotide polymorphisms (SNPs) in genes related to the immune response can influence susceptibility and severity of dengue. This study investigated the association of TNF-α rs361525 and IL-10 rs1800872 SNPs with susceptibility, severity, and clinical manifestations of dengue, correlating genotypes with symptoms, laboratory tests, and anthropometric variables.A total of 187 individuals residing in Goiânia were analyzed, including 92 cases and 95 controls. In the TNF-α rs361525 SNP, among the 46 cases, 92% were wild type, 4% were heterozygous, and 4% were mutants; among the 53 controls, 83% were wild type, 17% were heterozygous, and none were mutants. In the IL-10 rs1800872 SNP, among the 46 cases, 11% were wild type, 48% were heterozygous, and 41% were mutant; among the 42 controls, 21% were wild type, 58% were heterozygous, and 21% were mutant. The sample consisted of 61% females and 39% males. There was a significant association between the heterozygous+mutant genotypes of the TNF-α rs361525 SNP and the occurrence of thrombocytopenia (p = 0.000), indicating that genetic variations in the TNF-α and IL-10 genes may influence more severe clinical manifestations of dengue. The IL-10 rs1800872 SNP stood out for its ability to alter the expression of anti-inflammatory cytokines, impacting the immune balance and clinical evolution of the disease. The findings of this study contribute to the advancement of knowledge about the genetic factors involved in the immunopathogenesis of dengue and reinforce the potential of these SNPs as biomarkers for prognosis and therapeutic strategies. Early identification of genetically predisposed individuals can assist in epidemiological surveillance actions and in reducing morbidity and mortality associated with the disease.