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.