title: Loss-of-function polymorphisms in the filaggrin gene are associated with an increased susceptibility to chronic irritant contact dermatitis: a case-control study.
abstract: BACKGROUND
  Polymorphisms in the filaggrin (FLG) gene, which result in loss of filaggrin production, may alter the skin barrier and are a well-known predisposing factor for atopic dermatitis.
  
  
  OBJECTIVE
  As a compromised skin barrier and atopic dermatitis are risk factors for chronic irritant contact dermatitis (CICD), our objective was to determine whether polymorphisms in the FLG gene contribute towards susceptibility to occupational CICD.
  
  
  METHODS
  In a case-control study, the FLG polymorphisms R501X and 2282del4 were determined in 296 patients with CICD. Two hundred and seventeen apprentices in vocational training for high-risk occupations for CICD were chosen as controls. Data on skin diseases and conditions were collected by dermatologists from patients and by means of questionnaires from controls.
  
  
  RESULTS
  Heterozygotes for R501X and 2282del4, FLG null alleles, were more frequent among patients with CICD (12.5%) compared with controls (6.9%), resulting in an odds ratio of 1.91 (95% confidence interval 1.02-3.59). Among patients who were carriers of a FLG null allele, we found a higher lifetime prevalence of flexural eczema (62% vs. 46%; P = 0.04) and a higher atopy score (13 vs. 10 points; P = 0.05) compared with noncarriers. In the apprentice group, signs of dermatitis before the start of the vocational training were four times more prevalent in carriers (43%) than in noncarriers (10%; P < 0.001).
  
  
  CONCLUSIONS
  Our study shows that FLG null alleles are associated with increased susceptibility to CICD; whether or not the FLG null allele is an independent risk factor needs further study.
authors.affiliation: Coronel Institute of Occupational Health, Academic Medical Centre, University of Amsterdam, P.O. Box 22700, Amsterdam 1100 DE, the Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: de Jongh
authors.forename: L
authors.initials: L
authors.lastname: Khrenova
authors.forename: M M
authors.initials: MM
authors.lastname: Verberk
authors.forename: F
authors.initials: F
authors.lastname: Calkoen
authors.forename: F J H
authors.initials: FJ
authors.lastname: van Dijk
authors.forename: H
authors.initials: H
authors.lastname: Voss
authors.forename: S M
authors.initials: SM
authors.lastname: John
authors.forename: S
authors.initials: S
authors.lastname: Kezic
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D017453:Dermatitis, Irritant / Q000235:genetics*; D009783:Dermatitis, Occupational / Q000235:genetics*; D005260:Female; D000091344:Filaggrin Proteins; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins