Investigation of genetic susceptibility to Mycobacterium tuberculosis (VDR and IL10 genes) in a population with a high level of substructure in the Brazilian Amazon region

Abstract

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.

Association of Single-Nucleotide Polymorphisms in the VDR Gene with Tuberculosis and Infection of Beijing Genotype Mycobacterium tuberculosis

“…However, reports on the genes or SNPs associated with making human beings susceptible to tuberculosis development were inconsistent or contradictory due to the geographical restrictions and ethnic differences. 5 , 25 , 34 There were few reports on the susceptibility genes of tuberculosis in population from Xinjiang, China. 9 , 10 , 35 …”

“…The results showed that the distribution frequencies of alleles and genotypes of Fok I, Taq I, Apa I, Bsm I, rs3847987 and rs739837 in patients were not statistically different from that of the control group, which was inconsistent with the previously reported results. 5 , 6 , 39 For example, Sharma et al reported that Bsm I polymorphism appeared associated with the tuberculosis in tribes, castes and Muslims of central India, whereas, Taq I, Fok I and Apa I polymorphisms revealed association in general population and Muslims only. 40 The report in the Brazilian population found that Taq I-TT genotypes, Fok I-CC/(CC+CT) and Bsm I-GG genotypes were significantly associated with tuberculosis susceptibility, of which the homozygotes of Taq I-TT and Bsm I-GG both have approximately twofold increase in risk ratio than other genotypes.…”

“…The VDR gene is located on chromosome 12q13.11, and its Mendelian Inheritance Database (OMIM) number is 601769, including multiple single-nucleotide polymorphism sites such as FokI, TaqI, ApaI and BsmI. Previous literature shows that VDR gene polymorphisms can affect the host’s susceptibility to tuberculosis and the pharmacokinetic levels of first-line antitubercular drugs, 5–7 but the results did not reach a consensus in distinct ethnic groups. Sha et al 8 found that Bsm I-Bb and bb genotypes and Fok I-Ff and ff genotypes in VDR gene increasing the risk of tuberculosis susceptibility in adolescents.…”

Genetic Variants of MicroRNA and DROSHA Genes in Association With the Risk of Tuberculosis in the Amazon Population

“…Previous studies have revealed that deregulation of miRNAs and miRNA-related genes occur in many diseases ( de Souza et al, 2020 ; Silva et al, 2020 ). DROSHA initiates the biosynthesis of miRNAs by processing pri-miRNAs.…”

“…Recently, genetic variants in IL10, VDR, and microRNA genes were reported in subsequent studies in different human populations. However, there were few results of the association between these microRNA polymorphisms and tuberculosis susceptibility ( Song et al, 2013 ; Silva et al, 2020 ). The aim of this study was to perform an association study between SNPs in miRNA and DROSHA and tuberculosis and evaluate whether these selected SNPs may confer susceptibility or protection to TB in the Amazon population.…”