Alelos de HLA-ABDR genérico e variantes do gene TNFA em indivíduos com tuberculose

Abstract

Tuberculosis (Tb) is an infectious disease caused by mycobacteria of the complex Mycobacterium tuberculosis, being the species that most affects the man M. tuberculosis. The state of Amazonas has one of the highest incidence coefficients of Tb in Brazil, with 81,6 cases of Tb/100.000 inhabitants. In the capital Manaus, the figures are even more worrying because they present the incidence of 113,2 new cases of Tb/100.000 inhabitants. Tb is a disease associated with factors such as socioeconomic, nutritional, environmental and genetic profile of the host, as well as virulence of the bacillus. The genetic characteristics of individuals with Tb have often been explored, such as the HLA (Human Leukocyte Antigen) and SNVs (Single Nucleotide Variants) genes that regulate immune responses in several diseases. The present study aimed to evaluate the frequency of generic HLA alleles (A, B and DR) and SNVs of the TNFA gene, rs1799964 and rs1800610. HLA typing was performed by PCR-SSP (sequence specific primer) in 148 samples, 51 individuals with pulmonary Tb, 10 with extrapulmonary Tb and 87 controls. After the analysis, the HLA-A*29 was associated with Tb susceptibility (p= 0,0005; OR= 4,31; IC95%= 1,869 – 9,504), while HLA-A*31 (p= 0,0002; OR= 0,06; IC95%= 0,0057 – 0,3384), HLA-A*68 (p= 0,0175; OR= 0,122; IC95%= 0,0112 – 0,6990) e HLA-DRB1*14 (p= 0.027; OR= 0.248; IC95% = 0.0756 - 0.8162) were associated with Tb protection. Genotyping of SNV TNFA was performed by qPCR in 913 samples, being 355 individuals with pulmonary Tb, 86 individuals with extrapulmonary Tb and 472 controls. For the TNFA gene, only rs1800610 showed association with Tb in the following genetic models: dominant (p= 0.035; OR= 1.37; IC95% = 1.02-1.83), overdominant (p= 0.028; OR= 1.40; IC95% = 1.04-1.90) and log-Additive (p= 0.056; OR= 1.27; IC95% = 0.99-1.64). Our results suggest that HLA molecules may be associated with Tb, influencing the response to T lymphocytes, but as the HLA system is hyperpolymorphic, these results should be evaluated with caution. The TNFA gene, rs1800610, was associated with Tb susceptibility, which stimulates us to investigate the gene regions of the TNF-α signaling and production pathway, as well as the cytokines involved during infection by M. tuberculosis.