Objectives: Tuberculosis (TB) is an infectious and contagious disease that has been very influential in human history and presents high rates of mortality. The objective of this study was to investigate the association of VDR, IL10, and SLC11A1 gene polymorphisms with susceptibility to the presence of Mycobacterium tuberculosis infection. Methods: A total of 135 patients with confirmed TB and 141 healthy individuals were included in the analysis. Blood samples were collected for DNA extraction. Genotyping of the polymorphisms in the VDR and IL10 genes was performed by real-time PCR, and genotyping of the polymorphisms in the SLC11A1 gene by conventional PCR, followed by visualization in polyacrylamide gel. The genomic ancestry was obtained using an autosomal panel with 48 insertion/deletion ancestry-informative markers. Results: Polymorphisms TaqI (TT, p = 0.004), FokI (CC and CC + CT, p = 0.012 and p = 0.003, respectively), and BsmI (GG, p = 0.008) in the VDR gene, as well as A-592C (GC + AG, p = 0.001) in the IL10 gene, were significantly associated with susceptibility to TB In addition, high production of VDR combined with low production of IL10 showed protection for the TB group (p = 0.035). Conclusions: The VDR polymorphisms may confer an increased risk and the IL10 haplotype may be a protection factor for the presence of M. tuberculosis infection in the Brazilian population.

Background Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis and represents an important global public health issue. Single-nucleotide polymorphisms and INDELs are common genetic variations that can be located in genes associated with immune response and, therefore, they may have direct implications over the phenotype of susceptibility to infections like tuberculosis. This study aimed to investigate the association between the 17 genetic polymorphisms and susceptibility to tuberculosis in a Brazilian population. Methods This case-control study enrolled 283 individuals with active tuberculosis and 145 health care workers. Four INDELs and 13 single nucleotide polymorphisms and were genotyped using Multiplex PCR method and TaqMan SNP Genotyping Assays. Group comparisons for categorical variables were performed using the chi-squared test, whilst the t-Student test was used to analyze the continuous variables. Multiple logistic regression analyses were performed to estimate the odds ratio (OR) with 95% confidence intervals (CI). Deviation from Hardy-Weinberg equilibrium was assessed using chi-squared tests with Bonferroni correction. The results were analyzed comparing the genotypic distributions adopting the dominant model and the estimated values ​​of p corrected for multiple tests through FDR (False Discovery Rate) test. Results The HWE test confirmed that the genotypic frequencies for polymorphisms were balanced. The frequency of Del allele was 73 and 75%, in cases and controls respectively. Frequency of Del allele was significantly higher in the control group than TB group. The homozygous Del/Del genotype was present in 51.6% of cases and 58.6% of controls. The rare Ins/Ins genotype was present in only 7.6% of controls and 6% of cases. The ACE Del/Del genotype was significantly higher in the cases than in controls revealing significant protection for TB in the domain model (OR = 0.465; p < 0.005). Conclusions The Del/Del genotype of the rs4646994 in ACE gene was associated with susceptibility to tuberculosis. The identification of genetic variants responsible for susceptibility to tuberculosis will allow the development of new diagnostic tools for tuberculosis infection. These studies will help improve control and the future eradication of this disease.

Background: Tuberculosis is a global public health issue. Recent studies suggested association of host genetic factors to tuberculosis susceptibility in many populations. Polymorphisms can influence the host immune responses to tuberculosis. This study was designed to investigate the association of seventeen genetic polymorphisms with susceptibility and severity to tuberculosis in a sample of Brazilian population. Methods: This case-control study encompassed 283 active tuberculosis patients and 145 healthy subjects that had contact with the bacillus. Genotyping of 13 INDELs polymorphisms and 4 SNPs was achieved using Multiplex PCR method and TaqMan SNP Genotyping Assays. Results: Of the 17 investigated markers, only the ACE marker (rs4646994) showed significant differences between cases and controls. Conclusions: The DEL/DEL (deletion /deletion) genotype of the ACE marker configured a protection factor for the development of tuberculosis. As there is no data in the recent literature relating this polymorphism with tuberculosis in a Brazilian population, our study has become unprecedented.