title: Interplay of filaggrin loss-of-function variants, allergic sensitization, and eczema in a longitudinal study covering infancy to 18 years of age.
abstract: BACKGROUND
  Immune specific genes as well as genes regulating the formation of skin barrier are major determinants for eczema manifestation. There is a debate as to whether allergic sensitization and filaggrin gene (FLG) variants lead to eczema or FLG variants and eczema increase the risk of allergic sensitization. To investigate the time-order between eczema and allergic sensitization with respect to FLG variants, data from a large prospective study covering infancy to late adolescence were analyzed.
  
  
  RESULTS
  Repeated measurements of eczema and allergic sensitization (documented by skin prick tests) at ages 1, 2, 4, 10, and 18 years were ascertained in the Isle of Wight birth cohort (n = 1,456). Three transition periods were analyzed: age 1-or-2 to 4, 4 to 10, and 10 to 18 years. FLG variants were genotyped in 1,150 participants. Over the three transition periods, in temporal sequence analyses of initially eczema-free participants, the combined effect of FLG variants and allergic sensitization showed a 2.92-fold (95% CI: 1.47-5.77) increased risk ratio (RR) of eczema in subsequent examinations. This overall risk was more pronounced at a younger age (transition period 1-or-2 to 4, RR = 6.47, 95% CI: 1.96-21.33). In contrast, FLG variants in combination with eczema showed a weaker, but significant, risk ratio for subsequent allergic sensitization only up to 10 years of age.
  
  
  CONCLUSIONS
  Taking the time order into account, this prospective study demonstrates for the first time, that a combination of FLG variants and allergic sensitization increased the risk of eczema in subsequent years. Also FLG variants interacted with eczema and increased the risk of subsequent allergic sensitization, which, was limited to the younger age. Hence, early restoration of defective skin barrier could prevent allergic sensitization and subsequently reduce the risk of eczema development.
authors.affiliation: Department of Epidemiology and Biostatistics, Norman J Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Ziyab
authors.forename: Wilfried
authors.initials: W
authors.lastname: Karmaus
authors.forename: Mitra
authors.initials: M
authors.lastname: Yousefi
authors.forename: Susan
authors.initials: S
authors.lastname: Ewart
authors.forename: Eric
authors.initials: E
authors.lastname: Schauberger
authors.forename: John W
authors.initials: JW
authors.lastname: Holloway
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.forename: Syed Hasan
authors.initials: SH
authors.lastname: Arshad
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004485:Eczema / Q000235:genetics* / Q000276:immunology*; D005260:Female; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007223:Infant; D007231:Infant, Newborn; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D013997:Time Factors
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins