title: Paediatric-onset psoriasis is associated with ERAP1 and IL23R loci, LCE3C_LCE3B deletion and HLA-C*06.
abstract: BACKGROUND
  Recent genome-wide association studies have identified several genetic risk factors for psoriasis, but data on their association with age at onset are lacking.
  
  
  OBJECTIVE
  To compare the association between known risk alleles and psoriasis in well-defined cohorts with paediatric- and adult-onset psoriasis.
  
  
  METHODS
  Based on previous studies we selected seven genes and loci associated with psoriasis. Patients with paediatric-onset (< 18 years) and adult-onset psoriasis (≥ 18 years) and controls were genotyped. Genotype frequencies were compared between controls (n = 450) and all cases (n = 217), and between controls and cases stratified for confirmed age at onset (paediatric onset n = 80, adult onset n = 85).
  
  
  RESULTS
  Paediatric-onset psoriasis showed a significant association with single nucleotide polymorphisms in the ERAP1 (P = 0.042) and IL23R loci (P = 0.042), LCE3C_LCE3B-del (P = 0.003) and HLA-C*06 (P = 1.72 × 10(-19)) when compared with the control group. A significant association of these four genes was also demonstrated when all psoriasis cases were compared with controls. In adult-onset psoriasis a significant association was found for HLA-C*06 (P = 5.11 × 10(-6)) and for LCE3C_LCE3B-del (P = 0.042). No associations were found for the IFIH1, IL12B and TRAF3IP2 loci.
  
  
  CONCLUSIONS
  Notwithstanding the small cohort sizes, we demonstrated an association with established and recently discovered genetic risk factors in paediatric-onset psoriasis including genes involved in epidermal barrier function and adaptive immunity. Our data suggest that heritable factors may play a more important role in paediatric-onset psoriasis than in adult-onset psoriasis.
authors.affiliation: Department of Dermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands.
authors.forename: J G M
authors.initials: JG
authors.lastname: Bergboer
authors.forename: A M
authors.initials: AM
authors.lastname: Oostveen
authors.forename: M E A
authors.initials: ME
authors.lastname: de Jager
authors.forename: M
authors.initials: M
authors.lastname: den Heijer
authors.forename: I
authors.initials: I
authors.lastname: Joosten
authors.forename: P C M
authors.initials: PC
authors.lastname: van de Kerkhof
authors.forename: P L J M
authors.initials: PL
authors.lastname: Zeeuwen
authors.forename: E M G J
authors.initials: EM
authors.lastname: de Jong
authors.forename: J
authors.initials: J
authors.lastname: Schalkwijk
authors.forename: M M B
authors.initials: MM
authors.lastname: Seyger
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000626:Aminopeptidases / Q000235:genetics*; D016022:Case-Control Studies; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics*; D012307:Risk Factors
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; D015236:HLA-C Antigens; C515500:IL23R protein, human; C549748:LCE3B protein, human; C524768:LCE3C protein, human; D015778:Minor Histocompatibility Antigens; D018123:Receptors, Interleukin; D000626:Aminopeptidases; C464841:ERAP1 protein, human