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Title: Toll-like receptor-1 single-nucleotide polymorphism 1805T/G is associated with predisposition to multibacillary tuberculosis
Authors: Barletta-Naveca, Raphaela Honorato
Naveca, Felipe Gomes
Almeida, Vanessa Alves de
Porto, Jorge Ivan Rebelo
Silva, George Allan Villarouco da
Ogusku, Maurício Morishi
Sadahiro, Aya
Ramasawmy, Rajendranath
Boechat, Antonio Luiz
Keywords: Toll Like Receptor 1
Toll Like Receptor 2
Toll Like Receptor 4
Toll Like Receptor 9
1805tt Tlr1 Gene
Alcohol Consumption
Bacterium Identification
Case Control Study
Clinical Feature
Controlled Study
Disease Predisposition
Dna Extraction
Gene Frequency
Gene Sequence
Lung Tuberculosis
Major Clinical Study
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Sputum Culture
Issue Date: 2018
metadata.dc.publisher.journal: Frontiers In Immunology
metadata.dc.relation.ispartof: Volume 9, Número JUN
Abstract: Tuberculosis (TB), caused by mycobacterial species of the Mycobacterium tuberculosis complex, is a serious global health issue. Brazil is among the 22 countries with the highest number of TB cases, and the state of Amazonas has the highest incidence of TB cases in the country. Toll-like receptors (TLRs) are important pattern recognition receptors of the innate immunity and play a key role in orchestrating an effective immune response. We investigated whether the single-nucleotide polymorphisms (SNPs) 1805T/G TLR1, 2258G/A TLR2, 896A/G and 1196C/T of TLR4, 745T/C TLR6, and -1237A/G and -1486A/G of TLR9 are associated with the predisposition to TB and/or bacillary load. The SNPs genotyping was performed by nucleotide sequencing in 263 TB patients and 232 healthy controls residing in the state of Amazonas. Alleles and genotypes frequencies were similar between patients and healthy individuals for most of the investigated SNPs. Stratification of the TB patients according to their bacillary load showed that the genotype 1805TT TLR1 (rs5743618) was prevalent among paucibacillary patients [odds ratio (OR) = 0.38; 95% confidence interval (CI) = 0.19-0.76; p = 0.009] while the genotype 1805TG was common among multibacillary patients (OR = 3.72; CI = 1.65-8.4; p = 0.004). Comparison of demographic characteristics of patients to controls showed that TB is strongly associated with smoking (OR = 6.55; 95% CI = 3.2-13.6; p < 0.0001); alcohol use disorder (OR = 7.14; 95% CI = 3.7-13.9; p < 0.0001); and male gender (OR = 3.66; 95% CI = 2.52-5.3; p < 0.0001). Multivariate logistic regression demonstrated that alcoholism (OR = 2.93; 95% CI = 1.05-8.16; p = 0.03) and the 1805G allele (OR = 2.75; 95% CI = 1.33-5.7; p = 0.006) are predictive variables for multibacillary TB. Altogether, we suggest that the TLR1 1805G allele may be a relevant immunogenetic factor for the epidemiology of TB together with environmental, sociodemographic, and behavioral factors. © 2018 Barletta-Naveca, Naveca, Almeida, Porto, Silva, Ogusku, Sadahiro, Ramasawmy and Boechat.
metadata.dc.identifier.doi: 10.3389/fimmu.2018.01455
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