Arg753Gln polymorphism of the human Toll-like receptor 2 gene from infection to disease in pediatric tuberculosis

Dalgıç, Nazan; Tekin, Deniz; Kayaaltı, Zeliha; Söylemezoğlu, Tülın; Çakır, Erkan; Kılıç, Betül; Kutlubay, Büşra; Sancar, Mesut; Odabasi, Miyase

doi:10.1016/j.humimm.2011.02.001

Cited by 59 publications

(40 citation statements)

References 25 publications

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“…Additionally, the prevalence rates of genotypes and alleles, located within the analyzed TLR2 polymorphisms, as well as their associations with the occurrence of congenital HCMV infection, estimated in the current research, might have been due to the small sample size cohort of the studied offsprings. Likewise to our results, the prevalence rates of A allele in TLR2 2258 G>A SNP was determined to be low and a lack of AA homozygotes was also reported in other study groups, such as German, Finnish and Caucasian adults, or Turkish children [32, 48–50]. The heterozygotic status and A allele in TLR2 2258 G>A polymorphism were significantly more frequently identified among Turkish children with tuberculosis (TB) than in control cases [32].…”

Section: Discussionsupporting

confidence: 87%

“…Several studies had previously been performed to investigate the role of this polymorphism in pregnancy disorders, including preeclampsia, bacterial vaginosis, and preterm birth [28–31]. Moreover, the GA heterozygosity within TLR2 2258 polymorphism was shown to be involved in tuberculosis among Turkish children, as well as Candida sepsis in German adult patients [32, 33]. …”

Section: Introductionmentioning

confidence: 99%

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TLR2 2258 G>A single nucleotide polymorphism and the risk of congenital infection with human cytomegalovirus

Wujcicka

Paradowska

Studzińska

et al. 2017

Virol J

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BackgroundHuman cytomegalovirus (HCMV) is responsible for the most common intrauterine infections, which may be acquired congenitally from infected pregnant woman to fetus. The research was aimed to estimate the role of three single nucleotide polymorphisms (SNPs) located in TLR2 gene, and the common contribution of TLR2, and previously studied TLR4 and TLR9 SNPs, to the occurrence of congenital HCMV infection in fetuses and newborns.MethodsThe study was performed in 20 Polish fetuses and newborns, congenitally infected with HCMV, and in 31 uninfected controls, as well as with participation of pregnant women, the mothers of 16 infected and 14 uninfected offsprings. Genotypes in TLR2 SNPs were determined, using self-designed nested PCR-RFLP assays, and confirmed by sequencing. The genotypes were tested for Hardy-Weinberg (H-W) equilibrium, and for their relationship with the development of congenital cytomegaly, using a logistic regression model. The common influence of TLR2, TLR4 and TLR9 SNPs on the occurrence of congenital disease was estimated by multiple-SNP analysis.ResultsDistribution of the genotypes and alleles in TLR2 1350 T>C and 2029 C>T SNPs was similar between the studied groups of fetuses and neonates. In case of 2258 G>A polymorphism, the GA heterozygotic status was significantly more frequent in the infected cases than among the uninfected individuals (25.0% vs. 3.2%, respectively), and increased the risk of HCMV infection (OR 10.00, 95% CI 1.07–93.44; P ≤ 0.050). Similarly, the A allele within 2258 G>A polymorphism was significantly more frequent among the infected offsprings than in the uninfected ones (12.5% vs. 1.6%; P ≤ 0.050). Complex AA variants for both TLR2 2258 and TLR9 2848 G>A polymorphisms, were estimated to be at increased risk of congenital HCMV infection (OR 11.58, 95% CI 1.19–112.59; P ≤ 0.050). Additionally, significant relationships were observed between the occurrence of complex AA or GA variants for both TLR2 and TLR9 SNPs and the increased viral loads, determined in fetal amniotic fluids and in maternal blood or urine specimens (P ≤ 0.050).ConclusionsAmong various TLR2, TLR4 and TLR9 polymorphisms, TLR2 2258 G>A SNP seems to be an important factor associated with increased risk of congenital HCMV infection in Polish fetuses and neonates.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

TLR2 2258 G>A single nucleotide polymorphism and the risk of congenital infection with human cytomegalovirus

Wujcicka

Paradowska

Studzińska

et al. 2017

Virol J

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“…Several common polymorphisms associated with TB have been reported for different TLRs, including TLR1, -2, -4, -8, and -9 ( Table 1). The TLR2 variant R753Q appears to influence the progression of infection to TB disease in children (55). Another exonic SNP of TLR2 (597T/C) was found to be strongly associated with TB meningitis and miliary TB in Vietnam (226).…”

Section: Pattern Recognition Receptorsmentioning

confidence: 95%

Innate Immune Gene Polymorphisms in Tuberculosis

2012

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ABSTRACTTuberculosis (TB) is a leading cause worldwide of human mortality attributable to a single infectious agent. Recent studies targeting candidate genes and “case-control” association have revealed numerous polymorphisms implicated in host susceptibility to TB. Here, we review current progress in the understanding of causative polymorphisms in host innate immune genes associated with TB pathogenesis. We discuss genes encoding several types of proteins: macrophage receptors, such as the mannose receptor (MR, CD206), dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN, CD209), Dectin-1, Toll-like receptors (TLRs), complement receptor 3 (CR3, CD11b/CD18), nucleotide oligomerization domain 1 (NOD1) and NOD2, CD14, P2X7, and the vitamin D nuclear receptor (VDR); soluble C-type lectins, such as surfactant protein-A (SP-A), SP-D, and mannose-binding lectin (MBL); phagocyte cytokines, such as tumor necrosis factor (TNF), interleukin-1β (IL-1β), IL-6, IL-10, IL-12, and IL-18; chemokines, such as IL-8, monocyte chemoattractant protein 1 (MCP-1), RANTES, and CXCL10; and other important innate immune molecules, such as inducible nitric oxide synthase (iNOS) and solute carrier protein 11A1 (SLC11A1). Polymorphisms in these genes have been variably associated with susceptibility to TB among different populations. This apparent variability is probably accounted for by evolutionary selection pressure as a result of long-term host-pathogen interactions in certain regions or populations and, in part, by lack of proper study design and limited knowledge of molecular and functional effects of the implicated genetic variants. Finally, we discuss genomic technologies that hold promise for resolving questions regarding the evolutionary paths of the human genome, functional effects of polymorphisms, and corollary impacts of adaptation on human health, ultimately leading to novel approaches to controlling TB.

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“…We also found that TLR2 plays a key role in T regulatory cell (Treg) recruitment to the lungs and contributes significantly to maintaining the integrity of the tubercle granuloma in chronic infection (21). TLR2 polymorphisms, particularly within the TIR domain, have been associated with increased susceptibility to pulmonary tuberculosis (TB) and an increased risk of extrapulmonary TB (22–27). Analysis of a polymorphic guanine-thymine (GT) repeat located upstream of the TLR2 translational start site correlated shorter GT repeats with development of TB and lower TLR2 expression (28).…”

Section: Introductionmentioning

confidence: 99%

Divergent Functions of TLR2 on Hematopoietic and Nonhematopoietic Cells during Chronic Mycobacterium tuberculosis Infection

Konowich

Gopalakrishnan

Dietzold

et al. 2017

The Journal of Immunology

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We have reported that Toll-like receptor 2 (TLR2) is crucial for host resistance against chronic Mycobacterium tuberculosis (Mtb) infection; however, which cell types are key players in this response remain unknown. This led us to decipher the relative contribution of TLR2 on non-hematopoietic and hematopoietic cells in resistance against chronic Mtb infection in mice infected with Mtb Erdman. Consistent with our previous report, at 8 weeks of infection, TLR2KO→TLR2KO (TLR2KO) bone-marrow chimeric mice exhibited increased bacterial burden, disorganized accumulation of lymphocytes and mononuclear cells, and extensive pulmonary immunopathology compared to WT→WT (WT) chimeric mice. Bacterial burden and pulmonary immunopathology of chimeric mice lacking TLR2 in the hematopoietic compartment [TLR2KO→WT (H-TLR2KO)] was comparable to TLR2KO mice. In contrast, chimeric mice deficient in TLR2 in the non-hematopoietic compartment [WT→TLR2KO (NH-TLR2KO)] exhibited a marked attenuation in granulomatous inflammation compared to WT mice. Although NH-TLR2KO mice did not exhibit improved pulmonary bacterial control, significant reductions in bacterial burden in the draining lymph nodes, spleen, and liver were observed. These findings establish that the TLR2-mediated hematopoietic response promotes stable control of pulmonary bacterial burden and granuloma integrity, while TLR2 signaling on non-hematopoietic cells may partly facilitate granulomatous inflammation and bacterial dissemination.

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Arg753Gln polymorphism of the human Toll-like receptor 2 gene from infection to disease in pediatric tuberculosis

Cited by 59 publications

References 25 publications

TLR2 2258 G>A single nucleotide polymorphism and the risk of congenital infection with human cytomegalovirus

TLR2 2258 G>A single nucleotide polymorphism and the risk of congenital infection with human cytomegalovirus

Innate Immune Gene Polymorphisms in Tuberculosis

Divergent Functions of TLR2 on Hematopoietic and Nonhematopoietic Cells during Chronic Mycobacterium tuberculosis Infection

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