Effect of Toll-like receptor 4 gene polymorphisms on work-related respiratory symptoms and sensitization to wheat flour in bakery workers

Cho, Hyun Joo; Kim, Seung Hyun; Kim, Joo Hee; Choi, Hyunna; SON, J; Hur, Gyu Young; Park, Hae‐Sim

doi:10.1016/j.anai.2011.04.003

Cited by 29 publications

(22 citation statements)

References 32 publications

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“…In bakery workers, LPS in wheat flour could also interact with TLR4 to provoke airway inflammation [22]. Our previous study has shown that TLR4 expression is altered by TLR4 gene polymorphisms at -2027A→G and -1608T→C, which are associated with WRS in bakery workers [12]. In the present study, we demonstrated significant associations of TLR4 -1608 CC genotype and HT1 (GC) of TLR4 -2027A→G and -1608T→C with higher serum levels of S100A8 but not S100A9.…”

Section: Discussionmentioning

confidence: 99%

“…The two single nucleotide polymorphisms (SNP) of the TLR4 gene, -2027A→G and -1608T→C, were genotyped as previously described [12]. Briefly, genomic DNA was prepared from peripheral blood samples using a Puregene DNA purification kit (Qiagen, Germantown, Md., USA) and genotyped for the two SNP using the SNaPshot ddNTP primer extension method (Applied Biosystems, Foster City, Calif., USA).…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, genomic DNA was prepared from peripheral blood samples using a Puregene DNA purification kit (Qiagen, Germantown, Md., USA) and genotyped for the two SNP using the SNaPshot ddNTP primer extension method (Applied Biosystems, Foster City, Calif., USA). The primers used for amplification and extension have been described previously [12]. …”

Section: Methodsmentioning

confidence: 99%

“…Concomitantly, TLR4 can be activated by lipopolysaccharide (LPS), an endotoxin found in bakery flour dust, leading to the activation of monocytes, followed by the production of S100A8/S100A9 [7]. In our previous study, TLR4 genetic polymorphisms at -2027A→G and -1608T→C have been found to be associated with work-related symptoms (WRS) in bakery workers, indicating the involvement of innate immune responses in baker's asthma [12]. …”

Section: Introductionmentioning

confidence: 99%

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Serum S100A8 and S100A9 Enhance Innate Immune Responses in the Pathogenesis of Baker's Asthma

Pham

Yoon

Ban

et al. 2015

Int Arch Allergy Immunol

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Background: S100A8 and S100A9 can be produced by lipopolysaccharide-stimulated granulocytes and provoke an innate immune-mediated airway inflammation. Involvement of S100A8 and S100A9 has been implicated in asthma. To further understand the role of S100A8 and S100A9 during innate immune responses in baker's asthma, we investigated the associations of serum S100A8 and S100A9 with exposure to bakery allergens and polymorphisms of the Toll-like receptor 4 (TLR4) gene. Methods: Totally, 381 bakery workers and 100 unexposed healthy controls were recruited. Skin prick tests for bakery allergens were performed. Serum levels of S100A8, S100A9, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, and interleukin (IL)-8 were measured using ELISA. Predictive values of serum S100A8 and S100A9 in bakery workers were evaluated by receiver-operating characteristic (ROC) curves. Polymorphisms of TLR4 -2027A→G and -1608T→C were genotyped. Results: Higher serum levels of S100A8 and S100A9 were noted in bakery workers compared to the normal controls (p < 0.001); however, no significant differences were noted according to work-related symptoms. The area under the ROC curve of serum S100A8 was 0.886 for occupational exposure (p < 0.001). The TLR4 -1608CC genotype was significantly associated with a higher serum S100A8 level (p = 0.025). Serum S100A8 and S100A9 levels were correlated with serum levels of MPO (r = 0.396 and 0.189, respectively), TNF-α (r = 0.536 and 0.280, respectively), and IL-8 (r = 0.540 and 0.205, respectively; p < 0.001 for all). Conclusion: S100A8 and S100A9 are involved in innate immune responses under the regulation of TLR4 polymorphisms in baker's asthma pathogenesis. Serum S100A8 could be a potential biomarker for predicting occupational exposure to wheat flour in bakery workers.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Serum S100A8 and S100A9 Enhance Innate Immune Responses in the Pathogenesis of Baker's Asthma

Pham

Yoon

Ban

et al. 2015

Int Arch Allergy Immunol

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“…10,13,14 The capacity to mount an appropriate innate immune response to inflammatory stimuli is critical for host defense; therefore, defining the roles of TLR4 and CD14 in workers exposed to flour dust has been a recent focus in the field. 15,16 To address the role the innate immune response among subjects affected by rhinitis and baker asthma as well as in atopic and healthy (asymptomatic and nonatopic) subjects occupationally exposed to flour dust, we genotyped 167 study subjects for polymorphisms in TLR4 and CD14 and measured serum levels of cytokines and fractional exhaled nitric oxide (FeNO) to whether there is an association between these common innate immune polymorphisms and the development of allergic respiratory symptoms.…”

mentioning

confidence: 99%

Inflammatory Markers and Genetic Polymorphisms in Workers Exposed to Flour Dust

Marraccini

Cantone

Barretta

et al. 2016

Journal of Occupational &Amp; Environmental Medicine

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Biological and Genetic Markers in Occupational Asthma

Hur

Park

2014

Curr Allergy Asthma Rep

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Occupational asthma (OA) is a complex disease that is often hard to diagnose due to difficulties in detecting relevant exposure, along with inherent differences in disease susceptibility. Numerous studies have attempted to identify relevant biological and genetic markers for OA and to devise tools capable of detecting exposure to the causative agent. Immunological markers, including skin prick test reactivity and specific IgE and IgG antibodies can be used to detect high-molecular-weight allergens in cases of baker's asthma. For OA induced by low-molecular-weight agents, such as isocyanate, potential biomarkers include serum-specific IgE and IgG antibodies to isocyanate-HSA conjugate and IgG to cytokeratin 19 and transglutaminase-2. For protein-based markers, ferritin/transferrin and vitamin D-binding protein levels have been suggested for isocyanate-OA. Genetic markers of susceptibility to isocyanate-OA include human leukocyte antigen and CTNNA3. Further investigations will be needed to identify better biomarkers for OA, which may be used to inform clinical decision.

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Effect of Toll-like receptor 4 gene polymorphisms on work-related respiratory symptoms and sensitization to wheat flour in bakery workers

Cited by 29 publications

References 32 publications

Serum S100A8 and S100A9 Enhance Innate Immune Responses in the Pathogenesis of Baker's Asthma

Serum S100A8 and S100A9 Enhance Innate Immune Responses in the Pathogenesis of Baker's Asthma

Inflammatory Markers and Genetic Polymorphisms in Workers Exposed to Flour Dust

Biological and Genetic Markers in Occupational Asthma

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