ABSTRACT
The present study investigated the prevalence of the polymorphisms in the exon 1 of the MBL2 gene in patients with tuberculosis at a hospital in northern Brazil, which is a regional reference for the treatment of the disease. The study group was composed of 167 patients with tuberculosis, 34 of which had the extra-pulmonary form of the disease, while the other 133 had the pulmonary type. The control group consists of 159 healthy individuals. Samples of DNA extracted from leucocytes were submitted to Polymerase Chain Reaction for the amplification of a 120-bp segment of exon 1 of the MBL2 gene. The distribution of allele and genotype frequencies varied little among the different groups, and it was not possible to establish any clear association between the variants of the MBL2 gene and the susceptibility to or clinical profile of tuberculosis infections in the population analyzed.
Subject(s)
Mannose-Binding Lectin/genetics , Mycobacterium tuberculosis/growth & development , Tuberculosis, Pulmonary/genetics , Tuberculosis/genetics , Alleles , Brazil/epidemiology , Case-Control Studies , Exons , Female , Gene Frequency , Genotype , Humans , Male , Mannose-Binding Lectin/classification , Protein Isoforms/classification , Protein Isoforms/genetics , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis/microbiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/microbiologyABSTRACT
Regarding the importance of interferon-gamma (IFN-gamma) in protective immunity against Mycobacterium tuberculosis and the functional role of IFNG +874T/A single nucleotide polymorphism (SNP) in the IFN-gamma production, the present study investigated the relationship of this genetic polymorphism with susceptibility to tuberculosis (TB). A total of 129 patients with pulmonary tuberculosis (PTB), 33 with extrapulmonary tuberculosis (EPTB), and 156 control subjects were studied. Blood samples were drawn and plasma was used to measure IFN-gamma serum concentration by enzyme-linked immunoassay. DNA samples were extracted from leukocytes and used to investigate +874T/A polymorphism in IFNG gene using allele-specific oligonucleotide-polymerase chain reaction. An association between the presence of the allele +874A and the genotype +874AA with the active tuberculosis was found (p < 0.0001, 95% confidence interval = 1.64-3.22), at the same time that allele + 874T and genotype +874T/T were more frequent in the control group. The average plasma concentration of IFN-gamma among patients with tuberculosis was significantly lower than in the control group, and were lower in the EPTB group than in the group with PTB, suggesting a relationship of low plasma levels of this cytokine with active tuberculosis and the progression to more serious forms of the disease. Furthermore, we observed the association of the +874T/T and +874A/A genotypes with high and low IFN-gamma plasma concentrations, respectively, both in TB patients and in the control groups. Thus our findings suggest an association of the IFNG +874T/A polymorphism with susceptibility to M. tuberculosis infection in the studied population.
