title: Coexistence of 2282del4 FLG gene mutation and IL-18 -137G/C gene polymorphism enhances the risk of atopic dermatitis.
abstract: BACKGROUND
  Atopic dermatitis (AD) pathogenesis appears in the context of the correlation between cornified envelope proteins and immunological factors.
  
  
  OBJECTIVE
  To estimate the association between FLG R501X and 2282del4 gene mutations, -137 G/C IL-18 and -1112 C/T IL-13 gene polymorphisms and their influence on AD course and the risk in the Polish population.
  
  
  METHODS
  One hundred and fifty-two AD patients and 123 healthy volunteers were included into the study. Amplification refractory mutation system - polymerase chain reaction method was used.
  
  
  RESULTS
  2282del4 FLG mutation, predominant (p = 0.04) in Polish AD patients, enhanced the risk of AD (OR = 2.35; p = 0.01) and was associated with itch (p = 0.023). GG genotype of IL-18 was prevailing in AD (p < 0.0001), associated with elevated IgE levels (p = 0.00074) and pruritus (p < 0.0001). GG genotype and G-allele in -137 position of IL-18 increased AD risk (OR = 5.4; p = 0.0001, respectively, OR = 5.3; p = 0.000029). -1112 C/T polymorphism of IL-13 was associated with elevated IgE levels (p = 0.00049), pruritus (p = 0.0005), SCORAD score (p = 0.02), concomitant asthma (p = 0.0087) and AD risk (OR = 2.02; p = 0.012). Coexistence of 2282del4 or R501X FLG gene mutation with GG genotype of IL-18 was associated with a 6-fold higher risk of AD (OR = 5.8; p = 0.00013), contrary to combined occurrence of FLG mutations with T-allele in -1112 position of IL-13 gene (OR = 0.12; p = 0.1).
  
  
  CONCLUSIONS
  2282del4 FLG mutation similarly to GG genotype and G-allele in -137 position of IL-18 gene enhance the risk of AD in the Polish population. Coexistence of FLG mutations with GG genotype of IL-18 may be helpful to estimate chances of AD development.
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Trzeciak
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Gleń
authors.affiliation: Department of Forensic Medicine, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Rębała
authors.affiliation: Department of Radiological Science and Statistics, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Bandurski
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Sikorska
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Nowicki
keywords: atopic dermatitis; filaggrin; interleukin 13; interleukin 18