title: Lack of association between filaggrin gene mutations and onset of psoriasis in childhood.
abstract: BACKGROUND
  Atopic dermatitis (AD; OMIM#603165) and psoriasis (OMIM#177900) are two common inflammatory skin disorders. Both are genetically complex, multifactorial and do not follow a Mendelian pattern of inheritance. Both diseases share several genetic susceptibility loci such as the epidermal differentiation complex (EDC) on chromosome 1q21. Within the EDC, mutations in the filaggrin (FLG) gene are strongly associated with AD whereas no association has been replicated with psoriasis. However, reduced levels of filaggrin have been reported in psoriatic skin. Further, filaggrin deficiency was shown to be a modifying factor for the phenotype in another epidermal skin disorder, X-linked recessive ichthyosis. Altogether, this raises the question if FLG mutations may modify the disease course in other epidermal skin diseases such as psoriasis. Psoriasis is a highly heterogeneous disease and so far genetic studies have not taken the distinct sub-phenotype childhood onset into account.
  
  
  OBJECTIVE
  To determine if FLG mutations modify the onset of psoriasis.
  
  
  METHODS
  A total of 241 children with onset of psoriasis below 15 years of age and 314 healthy controls were identified at the Dermatology clinic, Karolinska University Hospital and diagnosed by the same dermatologist (JL). Blood samples were taken and medical history was recorded. FLG was genotyped in all patients and controls using allelic discrimination (n = 555) and sequencing (n = 20).
  
  
  CONCLUSIONS
  No association between FLG mutations and early onset of psoriasis was demonstrated (P = 0.57) and no novel mutations were detected, indicating that FLG loss-of-function variants do not have a strong effect on the onset of psoriasis in childhood.
authors.affiliation: Dermatology Unit, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. marten.winge@ki.se
authors.forename: M C G
authors.initials: MC
authors.lastname: Winge
authors.forename: J
authors.initials: J
authors.lastname: Suneson
authors.forename: J
authors.initials: J
authors.lastname: Lysell
authors.forename: P
authors.initials: P
authors.lastname: Nikamo
authors.forename: A
authors.initials: A
authors.lastname: Liedén
authors.forename: M
authors.initials: M
authors.lastname: Nordenskjöld
authors.forename: C F
authors.initials: CF
authors.lastname: Wahlgren
authors.forename: M
authors.initials: M
authors.lastname: Bradley
authors.forename: M
authors.initials: M
authors.lastname: Ståhle
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D005260:Female; D000091344:Filaggrin Proteins; D005838:Genotype; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011565:Psoriasis / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins