title: Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood.
abstract: Atopic dermatitis (AD) is a common disease with a complex etiology in childhood and adult life. A significant proportion of childhood AD is transient, but in many cases it persists into adulthood. We have recently shown that null mutations in the filaggrin gene (FLG) are an important predisposing factor for childhood eczema and eczema-associated asthma, but persistence to adulthood has not been analyzed. Here we studied a cohort of adult patients with persistent AD, which had been present since early childhood. In this cohort, the combined allele frequency of the two common FLG null variants was 0.270 (cf. population frequency 0.046). This represents an odds ratio of 7.7 with 95% confidence interval of 5.3-10.9 and a chi2 P-value of 1.7 x 10(-53). Our data conclusively demonstrate that identification of FLG null alleles is an indicator of a poor prognosis in AD, predisposing to a form of eczema that starts in early infancy and persists into adulthood. This study helps to further define the nature of the AD phenotype associated with FLG null alleles.
authors.affiliation: St John's Institute of Dermatology, King's College London, St Thomas's Hospital, London, UK. jonathan.barker@kcl.ac.uk
authors.forename: Jonathan N W N
authors.initials: JN
authors.lastname: Barker
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Zhao
authors.forename: Haihui
authors.initials: H
authors.lastname: Liao
authors.forename: Peter R
authors.initials: PR
authors.lastname: Hull
authors.forename: Simon P
authors.initials: SP
authors.lastname: Lee
authors.forename: Michael H
authors.initials: MH
authors.lastname: Allen
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Meggitt
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Reynolds
authors.forename: Richard C
authors.initials: RC
authors.lastname: Trembath
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015331:Cohort Studies; D003876:Dermatitis, Atopic / Q000235:genetics*; D004485:Eczema / Q000235:genetics*; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000502:physiology*; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D011379:Prognosis
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins