Avaliação dos polimorfismos em genes de TLR em pacientes com tuberculose

Abstract

Pulmonary tuberculosis (PTB) is an infectious disease caused by the mycobacteria of the Mycobacterium tuberculosis complex. Many immunological and genetic aspects still lack clarification about this disease, which includes the various possible outcomes that occur from the interaction of the pathogen with the host. In some people, the mechanisms of innate immunity eliminate the bacillus during primary infection, in others, an adaptive immune response develops that helps to contain the pathogen within granulomas initiated by innate immune cells. In order to contribute to the elucidation of factors still unknown about the immunogenetics of tuberculosis, the present study evaluated the presence of gene variants in Toll-like receptors in patients with pulmonary TB, as well as the associations between the presence of these variants with the highest chance of developing the disease. The association of TLR1 and TLR9 genotypes with the concentration of interleukin-6 (IL-6) was also evaluated. Single nucleotide variants (SNV) in TLR1 (rs5743618) and TLR9 (rs187084) genes in PTB patients were analyzed. Samples from healthy control subjects and patients with PTB recruited at the Policlínica Cardoso Fontes, in the city of Manaus, were genotyped by real-time quantitative PCR (qPCR). Both SNVs had a frequency higher than 10.0% in the studied population and were in Hardy-Weinberg equilibrium (EHW). There was an association of the SNV rs5743618 G/G genotype with protection against TBP (p=0.028; OR= 0.52; 95%CI= 0.28-0.95), and an association of the T allele of rs5743618 with the risk of PTB (p=0.017; OR=1.37; 95%CI=1.07-1.74). No significant allelic or genotypic differences were identified between the control and patient groups for the rs187084 variant of TLR9. For the quantification of IL-6, higher cytokine production was detected among patients, compared to the control group, however, there was no association of the studied genotypes with the production of IL-6. The present study highlights the functionality of the rs5743618 variant in PTB and corroborates several authors by highlighting IL-6 in the immunopathogenesis of PTB.