L.M.L. Montenegro, W.H.V. de Carvalho-Silva, A.S. Peixoto, R.H.T. Vasconcelos, A.L.A. do Nascimento and H.C. Schindler
Published April 20, 2024
Genet. Mol. Res. 23 (1): gmr19222
DOI http://dx.doi.org/10.4238/gmr19222
About the authors
L.M.L. Montenegro, W.H.V. de Carvalho-Silva, A.S. Peixoto, R.H.T. Vasconcelos, A.L.A. do Nascimento and H.C. Schindler
Corresponding author
W.H.V. de Carvalho-Silva
E-mail: wlissesveloso@gmail.com
ABSTRACT
Pulmonary tuberculosis (PTB) remains a major cause of morbidity and mortality in developing and high-burden countries, such as Brazil. The course of Mycobacterium tuberculosis infection is regulated by mainly two antagonistic cytokines that are produced and secreted by T cells, TNF-α and IL-10. Differences in TNFα and IL10 genes expression and protein production affected by single nucleotide polymorphisms (SNPs) have been demonstrated influence PTB susceptibility. Therefore, this study aimed to evaluate possible association between the functional polymorphisms of TNFα (- 308G/A, rs1800629) and IL10 (-1082A/G, rs1800896) cytokines with susceptibility to active PTB. A case-control study was carried out of 71 patients with active pulmonary tuberculosis (PTB+ group), 105 patients with nonspecific lung disease (TB-1 and TB-2 groups) and 101 clinically healthy individuals (healthy control) from reference public health hospitals in Pernambuco state (Northeast Brazil), to explore the association of cytokine polymorphismssociodemographic, clinical, and epidemiological variables with developing of PTB. TNFα -308G/A and IL10 -1082A/G genotyping was performed by TaqMan qPCR system. The univariate and logistic regression analyses demonstrated statistically association of male sex (OR=13.741, P<0,001) and age (OR=1.030, P=0.017) with PTB susceptibility, as risk factors. Regarding genetic variables, IL10 – 1082 G variant allele, AG and GG genotypes were also associated with developing of PTB as risk factors and maintained associated in the logistic regression dominant model (OR=7.998, P<0.001). Significant association was also observed between TNFα -308 GA genotype and PTB susceptibility, but as protective factor in univariate analysis (OR=0.375, P=0.005), and logistic regression dominant model associated the genotypes carrying A variant allele (OR=0.386, P=0.021). The study showed important role of IL10 and TNFα SNPs in developing PTB in a Brazilian population, being possible biomarkers for tuberculosis susceptibility.
Key words: Mycobacterium tuberculosis; SNP; Interleukin 10; Tumor Necrosis Factor alpha; PTB