title: Contact dermatitis in the construction industry: the role of filaggrin loss-of-function mutations.
abstract: BACKGROUND
  A high prevalence of contact dermatitis (CD) and respiratory symptoms has been observed in the construction industry, probably due to widespread exposure to irritants and allergens. It is unknown whether carriers of loss-of-function mutations in the gene encoding filaggrin (FLG), a known risk gene for eczema and asthma, are at increased risk.
  
  
  OBJECTIVE
  To investigate associations of FLG mutations with CD and respiratory symptoms in Dutch construction workers.
  
  
  METHODS
  A questionnaire including items on dermal and respiratory symptoms such as wheeze, shortness of breath and asthma was administered to construction workers. Total and specific serum IgE was analysed by enzyme immunoassays. Four FLG loss-of-function mutations were genotyped. CD was diagnosed by a team of a dermatologist and a clinical occupational medicine specialist using photographs of the subjects' hands and self-reported questionnaire data.
  
  
  RESULTS
  Of the 506 participating workers, 6·3% carried at least one FLG mutation. Mild CD was diagnosed by the specialists in 34·0%, and severe CD in an additional 24·3%. CD was considered work related in 282 of 295 subjects (95·6%). Carriers of FLG variants had an increased risk of CD compared with subjects carrying wild-type alleles [mild CD: odds ratio (OR) 5·71, 95% confidence interval (CI) 1·63-20·06; severe CD: OR 8·26, 95% CI 2·32-29·39]. FLG variants and the presence of CD were not associated with respiratory symptoms and atopy.
  
  
  CONCLUSIONS
  Contact dermatitis prevalence in construction workers is high. FLG loss-of-function mutations increase the risk of CD even further. FLG mutations were not associated with respiratory symptoms or atopy.
authors.affiliation: Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, the Netherlands.
authors.forename: J G
authors.identifier: http://orcid.org/0000-0001-5720-2226
authors.initials: JG
authors.lastname: Timmerman
authors.affiliation: Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, the Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Heederik
authors.affiliation: Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, the Netherlands.|Arbouw Research and Development, Harderwijk, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Spee
authors.affiliation: Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, the Netherlands.|Arbo Unie Expert Centre for Chemical Risk Management, Haarlem, the Netherlands.
authors.forename: F G
authors.initials: FG
authors.lastname: van Rooy
authors.affiliation: Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, the Netherlands.
authors.forename: E J M
authors.initials: EJ
authors.lastname: Krop
authors.affiliation: Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital and GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: G H
authors.initials: GH
authors.lastname: Koppelman
authors.affiliation: Department of Dermatology, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Rustemeyer
authors.affiliation: Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, the Netherlands.
authors.forename: L A M
authors.initials: LA
authors.lastname: Smit
mesh_terms: D000328:Adult; D000485:Allergens / Q000009:adverse effects; D059366:Asthma, Occupational / Q000453:epidemiology / Q000235:genetics; D060389:Construction Industry; D017453:Dermatitis, Irritant / Q000453:epidemiology / Q000235:genetics; D009783:Dermatitis, Occupational / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D012135:Respiratory Sounds / Q000235:genetics; D012307:Risk Factors; D057566:Self Report; D011795:Surveys and Questionnaires
chemical_list: D000485:Allergens; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins