Variantes en los factores de transcripción para IFN, TBET, STAT1, STAT4 y HLX y el riesgo de desarrollar tuberculosis pulmonar en un estudio de casos y controles de una población colombiana

Sánchez, Dulfary; Lefèbvre, Céline; García, Luis F.; Barrera, Luis F.

doi:10.7705/biomedica.v33i2.790

Cited by 4 publications

(1 citation statement)

References 58 publications

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“…showing no association between the SNP rs7574865 and pulmonary TB (Sánchez et al, 2013;Wu et al, 2018). Although the consistently negative results diminish the relevance of rs7574865 in relation to TB, its established functional significance and associations with other diseases suggest that its role cannot be definitively ruled out.…”

Section: Discussionmentioning

confidence: 91%

Association between STAT4 gene polymorphism and susceptibility to pulmonary tuberculosis in the Moldavian population

Varzari,

Tudor,

Corloteanu

et al. 2024

Int J Immunogenetics

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Signal transducer and activator of transcription 4 (STAT4) plays a crucial role in the host immune response against Mycobacterium tuberculosis. This study investigates the association between STAT4 gene polymorphisms and pulmonary tuberculosis (TB) risk in the Moldavian population. A total of 272 TB patients and 251 community‐matched controls underwent screening for functional single‐nucleotide polymorphisms (SNPs) rs897200 and rs7574865 in the STAT4 gene. The minor T allele and the TT/CT genotype of rs897200 demonstrated a significant association with reduced pulmonary TB risk (allelic model: adjusted OR = .74, p = .025; log‐additive model: adjusted OR = .72, p = .02; and dominant model: adjusted OR = .65, p = .023), indicating a protective effect. Similar associations, characterized by an even more pronounced reduction in risk, were observed among females and late‐onset TB patients (>44 years). No significant associations were found for rs7574865. In addition, a combined genotype analysis incorporating 43 SNPs from our previous studies revealed potential associations, such as STAT4 rs897200 CT with IFNG rs2430561 AA (adjusted OR = .36, p = .0025) and STAT4 rs897200 CT with TNFA rs1800629 GA (adjusted OR = .33, p = .0012). This study emphasizes the significant association of STAT4 rs897200 with pulmonary TB risk in the Moldavian population, underscoring its role in the disease development.

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Section: Discussionmentioning

confidence: 91%

Association between STAT4 gene polymorphism and susceptibility to pulmonary tuberculosis in the Moldavian population

Varzari,

Tudor,

Corloteanu

et al. 2024

Int J Immunogenetics

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Polymorphisms of the STAT4 gene in the pathogenesis of tuberculosis

Wang

et al. 2018

Bioscience Reports

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The signal transducer and activator of transcription 4 (STAT4) gene encodes a transcription factor that transmits signals induced by several cytokines which play critical roles in the development of autoimmune and chronic inflammatory diseases. In the present study, we have investigated the association between STAT4 polymorphisms and a predisposition to Mycobacterium tuberculosis (MTB) infection and pulmonary tuberculosis (PTB). In the present study, a total of 209 cases of PTB, 201 subjects with latent TB infection (LTBI), and 204 healthy controls (HC) were included. Logistic regression analyses were used to calculate P-values, odds ratios (ORs), and 95% confidence intervals (CIs) for assessing the association between single nucleotide polymorphisms (SNPs) and disease risk. We used Bonferroni correction to adjust the P-values. Genotyping was conducted using the improved multiplex ligase detection reaction (iMLDR) method. For the rs7574865 polymorphism, the GT genotype is less frequent in the LTBI group compared with HC (P=0.028, OR = 0.62; 95%CI: 0.40–0.95). In addition, the prevalence of the rs897200 CC genotype was lower in the PTB cases compared with LTBI individuals (P=0.039, OR = 0.54; 95%CI: 0.30–0.97). However, no SNPs within STAT4 were associated with PTB or LTBI after Bonferroni correction. Our study demonstrated that STAT4 variants were not related to LTBI and PTB.

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Variations in T cell transcription factor gene structure and expression associated with the two disease forms of sheep paratuberculosis

Nicol

Wilkie

Gossner

et al. 2016

Vet Res

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Two different forms of clinical paratuberculosis in sheep are recognised, related to the level of bacterial colonization. Paucibacillary lesions are largely composed of lymphocytes with few bacteria, and multibacillary pathology is characterized by heavily-infected macrophages. Analysis of cytokine transcripts has shown that inflammatory Th1/Th17 T cells are associated with development of paucibacillary pathology and Th2 cytokines are correlated with multibacillary disease. The master regulator T cell transcription factors TBX21, GATA3, RORC2 and RORA are critical for the development of these T cell subsets. Sequence variations of the transcription factors have also been implicated in the distinct disease forms of human mycobacterial and gastrointestinal inflammatory diseases. Relative RT-qPCR was used to compare expression levels of each transcript variant of the master regulators in the ileo-caecal lymph nodes of uninfected controls and sheep with defined paucibacillary and multibacillary pathology. Low levels of GATA3 in multibacillary sheep failed to confirm that multibacillary paratuberculosis is caused simply by a Th2 immune response. However, high levels of TBX21, RORC2 and RORC2v1 highlights the role of Th1 and Th17 activation in paucibacillary disease. Increased RORAv1 levels in paucibacillary tissue suggests a role for RORα in Th17 development in sheep; while elevated levels of RORAv4 hints that this variant might inhibit RORα function and depress Th17 development in multibacillary sheep.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-016-0368-3) contains supplementary material, which is available to authorized users.

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Variantes en los factores de transcripción para IFN, TBET, STAT1, STAT4 y HLX y el riesgo de desarrollar tuberculosis pulmonar en un estudio de casos y controles de una población colombiana

Cited by 4 publications

References 58 publications

Association between STAT4 gene polymorphism and susceptibility to pulmonary tuberculosis in the Moldavian population

Association between STAT4 gene polymorphism and susceptibility to pulmonary tuberculosis in the Moldavian population

Polymorphisms of the STAT4 gene in the pathogenesis of tuberculosis

Variations in T cell transcription factor gene structure and expression associated with the two disease forms of sheep paratuberculosis

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