title: Effect of Toll-like receptor 4 gene polymorphisms on work-related respiratory symptoms and sensitization to wheat flour in bakery workers.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Cho
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Joo-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Hyunna
authors.initials: H
authors.lastname: Choi
authors.forename: Jin-Kyeong
authors.initials: JK
authors.lastname: Son
authors.forename: Gyu-Young
authors.initials: GY
authors.lastname: Hur
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
mesh_terms: D000328:Adult; D000485:Allergens; D044466:Asian People / Q000235:genetics; D001249:Asthma / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D005260:Female; D005433:Flour / Q000009:adverse effects*; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D012220:Rhinitis / Q000453:epidemiology; D012882:Skin Tests; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D055815:Young Adult
chemical_list: D000485:Allergens; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4