Association of TNFα -308G/A and IL10 -1082A/G Polymorphisms with Pulmonary Tuberculosis Susceptibility in a Brazilian population

Abstract Pulmonary tuberculosis (PTB) remains a major cause of morbidity and mortality in developing countries. 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 a possible association between the functional polymorphisms of TNFα (-308G/A, rs1800629) and IL10 (-1082A/G, rs1800896) cytokines genes with susceptibility or resistance to active PTB in patients from Pernambuco state. We carried out a case-control study 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), to explore the association of cytokine polymorphisms, sociodemographic, 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; 95%CI = 5.794–32.589; P = < 0,001) and age (OR = 1.030; 95%CI = 1.005–1.055; 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 (OR = 2.777, 95%CI = 1.710–4.544, P = < 0.001; OR = 2.289, 95%CI = 1.095–4.849, P = 0.024; and OR = 6.572, 95%CI = 2.262–21.242, P = < 0.001, respectively), and maintained associated in the logistic regression dominant model (OR = 7.998, 95%CI = 2.719–23.519, P = < 0.001). Significant association was also observed between TNFα -308 GA genotype and PTB susceptibility, but as protector factor in univariate analysis (OR = 0.375, 95%CI = 0.179–0.766, P = 0.005), and logistic regression dominant model associated the genotypes carrying A allele variant (OR = 0.386, 95%CI = 0.172–0.865, 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.