Common polymorphisms in <i>TLR4</i> gene associated with susceptibility to pulmonary tuberculosis in the Sudanese

Zaki, Hani Yousif; Leung, Kim Hung; Yiu, Wai; Gasmelseed, Nagla; Elwali, Nasr Eldin; Yip, Shea Ping

doi:10.5588/ijtld.11.0517

Cited by 24 publications

(24 citation statements)

References 33 publications

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“…This finding adds another piece of information to the puzzle of PRR polymorphism in free-living rodents showing that recombination might be an important factor increasing TLR variability. Our results are consistent with studies of several other mammals reporting signals of recombination in the ECD in human TLR4 (Zaki et al 2012) or bovine TLR3, TLR4 and TLR10 (Seabury et al 2010). Detailed analysis of our sequences suggests that haplotypes H_2 and H_19 are recombinants composed of the ECD from haplogroup HG-IIm and ICD of HG-Im.…”

Section: Discussionsupporting

confidence: 93%

“…This applies especially to Tlr4 variation. As the genetic variation of human and livestock TLR4 is associated with susceptibility to various infectious and inflammatory diseases (e.g., Leveque et al 2003; Hawn et al 2005; Achyut et al 2007; Sentitula Kumar and Yadav 2012; Zaki et al 2012) and several nonsynonymous single nucleotide substitutions (nsSNP) has been identified as immunologically relevant (Ferwerda et al 2007), we focused on physical properties of the nsSNPs we detected in the house mouse Tlr4 . In total, we detected 15 nsSNP positions, which were distributed evenly across the whole sequenced region including the ECD, TMD, and ICD.…”

Section: Discussionmentioning

confidence: 99%

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Contrasting patterns of polymorphism and selection in bacterial‐sensing toll‐like receptor 4 in two house mouse subspecies

Fornůsková

Bryja

Vinkler

et al. 2014

Ecology and Evolution

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Detailed investigation of variation in genes involved in pathogen recognition is crucial for understanding co-evolutionary processes between parasites and their hosts. Triggering immediate innate response to invading microbes, Toll-like receptors (TLRs) belong presently among the best-studied receptors of vertebrate immunity. TLRs exhibit remarkable interspecific variation and also intraspecific polymorphism is well documented. In humans and laboratory mice, several studies have recently shown that single amino acid substitution may significantly alter receptor function. Unfortunately, data concerning polymorphism in free-living species are still surprisingly scarce. In this study, we analyzed the polymorphism of Toll-like receptor 4 (Tlr4) over the Palearctic range of house mouse (Mus musculus). Our results reveal contrasting evolutionary patterns between the two recently (0.5 million years ago) diverged house mouse subspecies: M. m. domesticus (Mmd) and M. m. musculus (Mmm). Comparison with cytochrome b indicates strong directional selection in Mmd Tlr4. Throughout the whole Mmd western Palaearctic region, a single variant of the ligand-binding region is spread, encoded mainly by one dominant haplotype (71% of Mmd). In contrast, Tlr4 in Mmm is much more polymorphic with several haplotypes at intermediate frequencies. Moreover, we also found clear signals of recombination between two principal haplogroups in Mmm, and we identified eight sites under positive selection in our dataset. Our results suggest that observed differences in Tlr4 diversity may be attributed to contrasting parasite-mediated selection acting in the two subspecies.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Contrasting patterns of polymorphism and selection in bacterial‐sensing toll‐like receptor 4 in two house mouse subspecies

Fornůsková

Bryja

Vinkler

et al. 2014

Ecology and Evolution

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“…Various host determinants such as sex, age and HIV co-infection influence the development of TB [4,5], and the clinical outcome of Mycobacterium tuberculosis infection has been mainly attributed to host factors [6-9]. However, there is a broad variation in clinical pathological manifestations of TB in both HIV positive and HIV negative patients, which cannot be explained exclusively by host or environmental factors.…”

Section: Introductionmentioning

confidence: 99%

Clinico-pathological features of tuberculosis due to Mycobacterium tuberculosis Uganda genotype in patients with tuberculous lymphadenitis: a cross sectional study

et al. 2014

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BackgroundTuberculous lymphadenitis is next to pulmonary tuberculosis as the most common cause of tuberculosis. Uganda genotype, one of the sub-lineages of Mycobacterium tuberculosis, is the most prevalent cause of pulmonary tuberculosis in Uganda. We here investigate the clinicopathological characteristics of patients with tuberculous lymphadenitis infected with M. tuberculosis Uganda genotype compared with those infected with M. tuberculosis non-Uganda genotype strains.MethodsBetween 2010 and 2012, we enrolled 121 patients (mean age 28.5 yrs, male 48%; female 52%) with tuberculous lymphadenitis, and categorized them by their M. tuberculosis genotypes. The clinical features and lymph node cytopathological parameters were compared between patients in the Uganda and non-Uganda categories using a crude and multivariable logistic regression model with adjustment for confounding factors.ResultsOf the 121participants, 56 (46%) were infected with strains of Uganda genotype. Patients infected with this genotype had significantly lower frequency of abdominal lymphadenopathy (odds ratio 0.4, p = 0.046) after adjusting for sex, age and HIV. Abdominal lymphadenopathy was also significantly associated with abnormal chest X-ray (p = 0.027).ConclusionTuberculous lymphadenitis patients infected with M. tuberculosis Uganda genotype were significantly less prone to have abdominal lymphadenopathy indicating potential reduced ability to disseminate and supporting the concept that differences in M. tuberculosis genotype may have clinical implications.

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“…TLR-knockout mouse studies indicate that TLR2, TLR4, and TLR9 participate to host resistance to Mtb infection (Bafica et al, 2005). Genetic variations of TLR1, TLR2, TLR4, TLR6 and TLR9 have been associated with the susceptibility to TB in different ethnic groups (OcejoVinyals et al, 2013;Thada et al, 2013;Zaki et al, 2012), but other studies have failed to demonstrate significant associations of TLRs polymorphisms with TB (Sanchez et al, 2012;Tian et al, 2013). Up to now, no previous studies have addressed the prevalence of TLRs polymorphisms in Egyptian patients with TB.…”

Section: Introductionmentioning

confidence: 99%

Association study of single nucleotide polymorphism of human Toll like receptor 9 and susceptibility to pulmonary tuberculosis in Egyptian population

Omran¹,

Kamel²,

Zakaria³

et al. 2016

Afr. J. Microbiol. Res.

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Toll-like receptors (TLRs) are known to play important roles in human innate immune systems. Polymorphisms in and functions of TLRs have been investigated to identify associations with specific infectious diseases including tuberculosis (TB). This study was performed for 166 samples of unrelated individual's diagnosis of pulmonary tuberculosis and 98 household healthy samples. Genomic DNA was extracted from EDTA-anticoagulated peripheral blood. The alleles of (rs352140) TLR9 gene polymorphisms were detected using polymerase chain reaction restriction fragment length polymorphism. The resulting fragments were separated in 3% agarose gel electrophoresis. The sequence results generated by the forward and reverse sequencing primers were analyzed with the software program sequencing analysis. Sequence comparisons of three genotypes AG, AA, and GG were performed using the multiple-alignment algorithm in Megalign. The direct counting was used to determine the allele and genotype frequencies of each polymorphism. Hardy-Weinberg equilibrium (HWE) tests were performed in controls by Fisher exact test. Significant deviations from the HardyWeinberg equilibrium in the distribution of the TLRs SNP genotypes in TB patients and controls were not detected for the SNP TLR9rs352140 for both patients and controls. These results do not indicate a major influence of these putative functional TLR SNP on the susceptibility to (or protection from) tuberculosis in Egyptian population.

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Common polymorphisms in TLR4 gene associated with susceptibility to pulmonary tuberculosis in the Sudanese

Cited by 24 publications

References 33 publications

Contrasting patterns of polymorphism and selection in bacterial‐sensing toll‐like receptor 4 in two house mouse subspecies

Contrasting patterns of polymorphism and selection in bacterial‐sensing toll‐like receptor 4 in two house mouse subspecies

Clinico-pathological features of tuberculosis due to Mycobacterium tuberculosis Uganda genotype in patients with tuberculous lymphadenitis: a cross sectional study

Association study of single nucleotide polymorphism of human Toll like receptor 9 and susceptibility to pulmonary tuberculosis in Egyptian population

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