Effect of Toll-like receptor 4 gene polymorphisms on work-related respiratory symptoms and sensitization to wheat flour in bakery workers
- Authors
- Cho, Hyun Joo; Kim, Seung-Hyun; Kim, Joo-Hee; Choi, Hyunna; Son, Jin-Kyeong; Hur, Gyu-Young; Park, Hae-Sim
- Issue Date
- 7월-2011
- Publisher
- ELSEVIER SCIENCE INC
- Citation
- ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY, v.107, no.1, pp.57 - 64
- Indexed
- SCIE
SCOPUS
- Journal Title
- ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY
- Volume
- 107
- Number
- 1
- Start Page
- 57
- End Page
- 64
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/112047
- DOI
- 10.1016/j.anai.2011.04.003
- ISSN
- 1081-1206
- Abstract
- Background: Bakery workers are exposed to flour allergens and endotoxins, which interact to induce allergic responses and respiratory symptoms. We hypothesized that Toll-like receptor 4 (TLR4) may be involved in the development of work-related respiratory symptoms and sensitization to wheat flour. Objective: To investigate the genetic contribution of TLR4 to respiratory symptoms and sensitization to wheat flour in bakery workers, we performed a genetic association study of TLR4 in Korean bakery workers. Methods: A total of 381 workers completed a questionnaire regarding work-related symptoms. Skin prick tests with common and occupational allergens were done, and specific antibodies to wheat flour were measured by enzyme-linked immunosorbent assay. Two single-nucleotide polymorphisms (SNPs) of the TLR4 gene (-2027A>G and -1608T>C) were genotyped, and the functional effects of the polymorphisms were analyzed using the luciferase reporter and electrophoretic mobility shift assay. Results: Homozygotes for the -2027G and -1608C alleles exhibited a lower prevalence of work-related lower respiratory symptoms than carriers of the -2027AA/AG (P = .007) and -1608TT/TC (P = .021) genotypes. Furthermore, haplotype analysis indicated that workers with the haplotype 2, ht2 [GC], had fewer work-related lower respiratory symptoms (P = .021). The ht2 [GC] construct showed lower promoter activity than the haplotype 1, ht1 [AT], in both BEAS-2B (P = .001) and U937 cells (P = .007). Conclusion: Bakery workers carrying the TLR4 variants are at lower risk of developing work-related chest symptoms. This finding suggests that the TLR4 gene may be involved in allergic sensitization to wheat flour as well as endotoxin-induced respiratory symptoms in endotoxin-allergen exposed workers and that carriers of TLR4 variants are less affected by environmental exposure.
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