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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.

Authors
Cho, HJ; Kim, SH; Kim, JH; Choi, H; Son, JK; Hur, GY; Park, HS
Citation
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 107(1):57-64, 2011
Journal Title
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology
ISSN
1081-12061534-4436
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.
MeSH terms
AdultAllergens/diagnostic useAsian Continental Ancestry Group/geneticsAsthma/epidemiology/etiology/*geneticsFemaleFlour/*adverse effectsGenetic Association StudiesHaplotypesHumansMaleMiddle AgedOccupational Diseases/epidemiology/etiology/*geneticsPolymorphism, GeneticPrevalenceRhinitis/epidemiologySkin TestsToll-Like Receptor 4/*geneticsYoung Adult
DOI
10.1016/j.anai.2011.04.003
PMID
21704886
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Journal Papers > Research Organization > Regional Clinical Trial Center
AJOU Authors
김, 승현박, 해심
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