Genetic polymorphism in association with susceptibility to tuberculosis: a study in a Pakistani population

Aslam, Muhammad; Khan, Asaad; Rasul, Sumaira; Manzoor, Hamid; Iqbal, Rehana; Ahmed, Shehzad; Ali, Muhammad

doi:10.1007/s42770-019-00048-8

Cited by 5 publications

(5 citation statements)

References 38 publications

(36 reference statements)

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“…[ 5 ] Nowadays, many researchers have studied the field of TB pathogenesis at the genetic level, such as single nucleotide polymorphisms. [ 6 , 7 ] However, key genes associated with TB have not been reported until now. Thus, our study uses online bioinformatics data to explore differentially expressed genes (DEGs) between TB and healthy controls.…”

Section: Introductionmentioning

confidence: 99%

“…Expression profiling by array plays an important role in the field of molecular biology and it can simultaneously detect thousands of genes [5] . Nowadays, many researchers have studied the field of TB pathogenesis at the genetic level, such as single nucleotide polymorphisms [6,7] . However, key genes associated with TB have not been reported until now.…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive analyses of potential key genes in active tuberculosis

et al. 2021

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Background: Tuberculosis (TB) is a global health problem that brings us numerous difficulties. Diverse genetic factors play a significant role in the progress of TB disease. However, still no key genes for TB susceptibility have been reported. This study aimed to identify the key genes of TB through comprehensive bioinformatics analysis.Methods: The series microarray datasets from the gene expression omnibus (GEO) database were analyzed. We used the online tool GEO2R to filtrate differentially expressed genes (DEGs) between TB and health control. Database for annotation can complete gene ontology function analysis as well as Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Protein-protein interaction (PPI) networks of DEGs were established by STRING online tool and visualized by Cytoscape software. Molecular Complex Detection can complete the analysis of modules in the PPI networks. Finally, the significant hub genes were confirmed by plug-in Genemania of Cytoscape, and verified by the verification cohort and protein test.Results: There are a total of 143 genes were confirmed as DEGs, containing 48 up-regulated genes and 50 down-regulated genes. The gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis show that upregulated DEGs were associated with cancer and phylogenetic, whereas downregulated DEGs mainly concentrate on inflammatory immunity. PPI networks show that signal transducer and activator of transcription 1 (STAT1), guanylate binding protein 5 (GBP5), 2 0 -5 0 -oligoadenylate synthetase 1 (OAS1), catenin beta 1 (CTNNB1), and guanylate binding protein 1 (GBP1) were identified as significantly different hub genes. Conclusion:We conclude that these genes, including TAT1, GBP5, OAS1, CTNNB1, GBP1 are a candidate as potential core genes in TB and treatment of TB in the future.Abbreviations: CTNNB1 = catenin beta 1, DEG = differentially expressed gene, GBP1 = guanylate binding protein 1, GBP5 = guanylate binding protein 5, GEO = gene expression omnibus, GO = gene ontology, IFI44 = interferon-induced protein 44 like, KEGG = Kyoto Encyclopedia of Genes and Genomes, MTB = Mycobacterium tuberculosis, OAS1 = 2 0 -5 0 -oligoadenylate synthetase 1, OAS2 = 2 0 -5 0 -oligoadenylate synthetase 2, OAS3 = 2 0 -5 0 -oligoadenylate synthetase 3, PARP9 = poly(ADP-ribose) polymerase family member 9, PPI = protein-protein interaction , SOCS3 = suppressor of cytokine signaling 3, STAT1 = signal transducer and activator of transcription 1, TB = tuberculosis, XAF1 = XIAP associated factor 1.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive analyses of potential key genes in active tuberculosis

et al. 2021

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“…The organism is an aerobic pathogenic bacterium that typically causes respiratory infection. TB displays epidemic cycles that might, rarely, last for centuries [1].…”

Section: Introductionmentioning

confidence: 99%

Multidrug-resistant strains of Mycobacterium complex species in Egyptian farm animals, veterinarians, and farm and abattoir workers

et al. 2020

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Background and Aim: Mycobacterium tuberculosis complex (MTBC) is a group of mycobacteria that are important human pathogens. Mycobacterium tuberculosis and Mycobacterium bovis cause serious chronic life-threatening disease and also significant economic losses in both production and remedication. Recently, emergence of multidrug-resistant tuberculosis (MDR-TB) complex has generated global recognition of the need for rapid and sensitive diagnosis and development of new treatments. The current study illustrates the isolation/identification of MTBC strains in specimens obtained from cows and humans by conventional and real-time polymerase chain reaction (RT-PCR) techniques. Further, the study assesses sensitivity to antituberculosis drugs in isolated MDR strains. Materials and Methods: A total of 1464 samples from cattle (1285 raw milk and 179 lymph node), and 149 human sputum samples, were collected from farms and abattoirs in Delta Egypt. Conventional methods (culture and Ziehl–Neelsen staining) were implemented as were RT-PCR using MTBC universal DNA. The effect of some antituberculosis drugs on obtained isolates was assayed using drug susceptibility proportion and qualitative suspension techniques. Results: The MBTC detection rate using the culture method was higher than for Ziehl–Neelsen staining; raw cow milk (2.56 vs. 1.63%), lymph nodes (51.59 vs. 48.04%), and human sputum (5.36 vs. 4.02%). A total of 135 isolates were obtained. Application of RT-PCR detected 138 isolates from the same set of samples. MBTC isolates were resistant to first-line antituberculosis drugs, such as pyrazinamide, isoniazid, rifampicin, and ethambutol by 78.5, 59.3, 40.7, and 31.8%, respectively, and could be highly resistant to kanamycin (82.3%) and amikacin (80.7%). However, isolates remained sensitive to ciprofloxacin (71.1%) and clarithromycin (73.3%) as second-line drugs. Conclusion: There is a growing risk for isolation of MDR-TB from raw milk and lymph nodes of field tuberculin positive cattle as well as sputum of veterinarians and workers existed in farms and abattoirs. PCR-based techniques have become the gold standard for the identification of mycobacterial species, showing high efficiency compared to bacteriological and microscopic examination. Application of the first- and second-line antituberculosis drugs in combination could counter the MDR-TB concern once infections are identified.

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“…This implied that IL-35 was closely involved in the pathogenesis of PTB; hence, it was very necessary to explore the relationship between IL-3 5 gene variation and PTB genetic susceptibility. Previous studies found that the IL-3 5 rs4740 variant showed a significant relationship with a decreased risk for PTB ( 30 ), while the rs568408 variant was not related to PTB risk ( 31 ). Nevertheless, our study found no significant association between rs2243123, rs2243135, rs568408, rs428253, rs4740, and rs9807813 variants in the IL-35 gene and PTB susceptibility.…”

Section: Discussionmentioning

confidence: 97%

The effects of IL-27 and IL-35 gene variation and expression levels on the susceptibility and clinical manifestations of pulmonary tuberculosis

Gao,

Xiong,

Liang

et al. 2024

Front. Immunol.

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Inflammatory cytokines have crucial roles in the pathogenesis of tuberculosis (TB), and interleukin (IL)-27 and IL-35 have a pro-inflammatory and anti-inflammatory effect on many diseases, including infectious diseases. Therefore, we evaluated the relationship between IL-27 and IL-35 gene polymorphism, expression levels, and pulmonary TB (PTB) susceptibility. Nine single-nucleotide polymorphisms (SNPs) in the IL-27 gene (rs181206, rs153109, and rs17855750) and the IL-35 gene (rs4740, rs428253, rs9807813, rs2243123, rs2243135, and rs568408) were genotyped by the SNPscan technique in 497 patients with PTB and 501 controls. There was no significant difference regarding the genotype and allele frequencies of the above SNPs in the IL-27 and IL-35 genes between patients with PTB and controls. Haplotype analysis showed that the frequency of the GAC haplotype in the IL-35 gene was significantly decreased in patients with PTB when compared to controls (p = 0.036). Stratified analysis suggested that the frequency of the IL-27 rs17855750 GG genotype was significantly increased in patients with PTB with fever. Moreover, the lower frequency of the IL-35 rs568408 GA genotype was associated with drug-induced liver injury in patients with PTB. The IL-35 rs428253 GC genotype, as well as the rs4740 AA genotype and A allele, showed significant relationships with hypoproteinemia in patients with PTB. When compared with controls, the IL-27 level was significantly increased in patients with PTB. Taken together, IL-35 gene variation might contribute to a protective role on the susceptibility to PTB, and IL-27 and IL-35 gene polymorphisms were associated with several clinical manifestations of patients with PTB.

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Genetic polymorphism in association with susceptibility to tuberculosis: a study in a Pakistani population

Cited by 5 publications

References 38 publications

Comprehensive analyses of potential key genes in active tuberculosis

Comprehensive analyses of potential key genes in active tuberculosis

Multidrug-resistant strains of Mycobacterium complex species in Egyptian farm animals, veterinarians, and farm and abattoir workers

The effects of IL-27 and IL-35 gene variation and expression levels on the susceptibility and clinical manifestations of pulmonary tuberculosis

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