title: Filaggrin null alleles are not associated with psoriasis.
abstract: Psoriasis is a common skin disease with an etiology consistent with a multifactorial trait. Several psoriasis susceptibility loci are known, a number of which are also implicated in a predisposition to atopic dermatitis (AD), including the epidermal differentiation complex on chromosome 1q21. It has recently been shown in several replicate studies that prevalent null alleles for the filaggrin gene (FLG) on 1q21 are an important genetic factor in AD. Here, we examined the role of these FLG variants in psoriasis using case:control association studies comparing Irish and UK psoriasis cohorts (combined n=691) to ethnically matched populations (combined n=2117). No association was present for the two common European FLG mutations R501X and 2282del4 (combined chi2 P=0.989). In addition, the 3' end of the FLG open-reading frame was sequenced in a number of patients with differing types of psoriasis (plaque, guttate, palmoplantar, and late-onset), which excluded the possibility of a gain-of-function frameshift mutation such as those found in loricrin or certain keratin genes. These data suggest that FLG mutations are unlikely to be involved in genetic susceptibility to psoriasis and implies that there may be within-locus heterogeneity in chromosomal regions involved in both AD and psoriasis.
authors.affiliation: Epithelial Genetics Group, Human Genetics Unit, Division of Pathology and Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ana
authors.initials: A
authors.lastname: Terron-Kwiatkowski
authors.forename: Haihui
authors.initials: H
authors.lastname: Liao
authors.forename: Simon P
authors.initials: SP
authors.lastname: Lee
authors.forename: Michael H
authors.initials: MH
authors.lastname: Allen
authors.forename: Peter R
authors.initials: PR
authors.lastname: Hull
authors.forename: Linda E
authors.initials: LE
authors.lastname: Campbell
authors.forename: Richard C
authors.initials: RC
authors.lastname: Trembath
authors.forename: Francesca
authors.initials: F
authors.lastname: Capon
authors.forename: Christopher E M
authors.initials: CE
authors.lastname: Griffiths
authors.forename: David
authors.initials: D
authors.lastname: Burden
authors.forename: Ross
authors.initials: R
authors.lastname: McManus
authors.forename: Rosalind
authors.initials: R
authors.lastname: Hughes
authors.forename: Brian
authors.initials: B
authors.lastname: Kirby
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Rogers
authors.forename: Oliver
authors.initials: O
authors.lastname: Fitzgerald
authors.forename: David
authors.initials: D
authors.lastname: Kane
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: Alan D
authors.initials: AD
authors.lastname: Irvine
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
mesh_terms: D000328:Adult; D003876:Dermatitis, Atopic / Q000235:genetics; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D011565:Psoriasis / Q000235:genetics*
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins