Polimorfismo do gene TOLLIP (rs5743899) em pacientes com tuberculose pulmonar

Abstract

New cases of tuberculosis (TB) have been increasing in Amazonas, in 2016, it was about 67.2 cases of TB/100 thousand inhabitants, the highest in the country. Socioeconomic factors may be one of the explanations for this high rate. However, genetic factors can influence the immune response to the pathogen. In this context, polymorphisms in TOLLIP genes may be involved with immunological alterations in the response to Mycobacterium tuberculosis, since studies have shown that the protein associated with Toll-like receptors plays a regulatory role in intracellular signaling, mainly in macrophages and dendritic cells, exerting a negative feedback on the release of pro-inflammatory cytokines such as IL-6 and TNF through the MyD88 pathway, as well as influencing the secretion of IL1β through the inflammasome, fundamental responses in the innate immune defense against pathogens, including Mycobacterium tuberculosis. Thus, single-base polymorphisms (SNPs) in TOLLIP genes (rs5743899) were investigated, focusing on pulmonary TB patients and controls. For this study, a total of 547 samples were evaluated, distributed in: 251 samples from patients with pulmonary TB, and 296 control subjects. Genotyping for TOLLIP (rs5743899) was performed by PCR. After analyzing the results of the frequency of alleles and genotypes, there was no association for a greater chance of risk or not for TB, which differs from studies carried out in other populations. We also evaluated TOLLIP (rs5743899) genotypes (AA and AG) versus IL1-β concentrations in 67 plasma samples from patients (n=30) and controls (n=37), but no relationship between genotypes with the concentration of IL1-β. In the present study, no association of TOLLIP genes (rs5743899) with TB was observed, but this study should be expanded to include other TOLLIP gene regions, considering the crucial role of tollip protein in regulating the inflammatory response in tuberculosis.