title: Filaggrin loss-of-function mutations, atopic dermatitis and risk of actinic keratosis: results from two cross-sectional studies.
abstract: BACKGROUND
  Common loss-of-function mutations in filaggrin gene (FLG) represent a strong genetic risk factor for atopic dermatitis (AD). Homozygous mutation carriers typically display ichthyosis vulgaris (IV) and many have concomitant AD. Previously, homozygous, but not heterozygous, filaggrin gene mutations have been associated with squamous cell carcinomas.
  
  
  OBJECTIVE
  The first objective was to examine the association between FLG mutations and actinic keratosis (AK). The second objective was to investigate the occurrence of AK in patients with IV and AD, respectively.
  
  
  METHODS
  FLG mutation status in patients with AK was compared with controls from the general population. Furthermore, based on nationwide data from Danish registers, we compared the risk of AK in patients with IV, AD and psoriasis, respectively.
  
  
  RESULTS
  The prevalence of homozygous FLG mutations was significantly higher in the AK group (n = 4, 0.8%) in comparison with the control group (n = 18, 0.2%), whereas the prevalence of heterozygous FLG mutations was lower. In hospital registry data, patients with AD exhibited an increased risk of AK than did psoriasis controls (adjusted OR 1.46; [95% CI 1.12-1.90]), whereas no difference in risk was observed between patients with IV and AD.
  
  
  CONCLUSIONS
  This study indicates an increased susceptibility to AK in individuals with homozygous, but not heterozygous, FLG mutations and in patients with AD compared to psoriasis. Whether a reduction or absence of epidermal filaggrin could contribute to the susceptibility to AK in patients with IV and AD is unknown and additional research is needed to further explore this relationship.
authors.affiliation: Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Y M F
authors.initials: YMF
authors.lastname: Andersen
authors.affiliation: Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Egeberg
authors.affiliation: Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Balslev
authors.affiliation: Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: C L T
authors.initials: CLT
authors.lastname: Jørgensen
authors.affiliation: Department of Clinical Biochemistry, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: P B
authors.initials: PB
authors.lastname: Szecsi
authors.affiliation: Department of Clinical Biochemistry, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Stender
authors.affiliation: Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Kaae
authors.affiliation: Research Centre for Prevention and Health, the Capital Region of Denmark, Copenhagen, Denmark.|Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Linneberg
authors.affiliation: Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: G
authors.initials: G
authors.lastname: Gislason
authors.affiliation: Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Skov
authors.affiliation: Dermatology Service, Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, CA, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Elias
authors.affiliation: Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: J P
authors.initials: JP
authors.lastname: Thyssen
mesh_terms: D003430:Cross-Sectional Studies; D003876:Dermatitis, Atopic / Q000235:genetics*; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D055623:Keratosis, Actinic / Q000235:genetics*; D009154:Mutation
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins