Avaliação de polimorfismos de base única (SNP) em genes do inflamassoma e componentes relacionados em pacientes com tuberculose

Abstract

Tuberculosis (TB) is an infectious disease caused by the Mycobacterium tuberculosis complex and it is considered the first and leading to cause of death by single infectious agent according to the World Health Organization. In 2017, about 1.3 million deaths and 10 million of new cases occurred worldwide causing TB. In the same year, the incidence rate in the state of Amazonas was 74.1/100 thousand inhabitants, the highest in the country. This scenario confirms TB remains a public health problem. Among infected individuals 10% develop active TB. In view of this fact, genetic factors of the host can contribute and trigger different immune responses to bacilli. The innate immune response is the first line of defense against several microorganisms, including mycobacteria. During infection, intracellular protein complexes known as inflammasome are activated and they are essential for controlling bacterial growth through the activation and secretion of proinflammatory cytokines such as IL-1β and IL-18. In this context, polymorphisms in genes of inflammasome may result in different responses to infection. In addition, immunogenic studies in inflammasomes in the northern region are still considered rare. Therefore, the present study evaluated single nucleotide polymorphisms (SNPs) in inflammatory genes NLRP1 (rs35865013), NLRP3 (rs3806265) and AIM2 (rs1103577) and related components CARD8 (rs2009373) and CTSB (rs1692816) in patients with TB. In this study, were included 434 patients with pulmonary TB (TB), 143 patients with extrapulmonary TB (TB) and 549 controls (contacts) recruited from Reference Center for Sanitary Pneumology ''Policlínica Cardoso Fontes‟, Manaus-AM, Brazil. The determination of IL-1β concentrations was performed by ELISA in samples of TBP (n=30), TBE (n=20) and controls (n=30). SNP CTSB rs1692816 was associated with protective of ETB vs PTB (p: 0.027, OR: 0.53) and after that adjusted for sex and age (p: 0.02; OR: 0.50; 95% CI: 0.27 0.94). SNPs had a frequency greater than 10.0% in the study population. The rs1103577 SNP TT genotype in the AIM2 gene was observed for male protection in patients with TBP (p=0.027 and OR=0.69, pajust = 0.051 and OR = 0.68). There was a significant difference in the concentration of IL-1β in the AA genotype of the CTSB gene rs1692816, suggesting that individuals with this genotype present a better response of the innate immunity against the TB bacillus. The results of this study increasingly reinforce the importance of inflammasomes in TB, contributing to a better understanding of the mechanisms involved in the immune response of the host and thus elucidating the factors associated with protection and risk for TB that justify such high coefficients of the disease in the Amazonas.