title: Loss-of-function variants of the filaggrin gene are not major susceptibility factors for psoriasis vulgaris or psoriatic arthritis in German patients.
abstract: Psoriasis vulgaris and atopic dermatitis share a number of features such as chronic cutaneous inflammation and disturbed epidermal barrier function. Genome-wide scans have revealed a conspicuous overlap of susceptibility loci for both diseases involving chromosomal regions 1q21, 3q21, 17q25, and 20p12. Recently, two loss-of-function variants in the gene encoding filaggrin at 1q21 were shown to be strongly associated with atopic dermatitis. In view of a possible genetic overlap of the two skin diseases, we investigated 375 patients suffering from psoriasis vulgaris, 375 patients with psoriatic arthritis, and 376 control probands. Moreover we directly studied expression of filaggrin in 10 patients suffering from psoriasis vulgaris. Our immunohistochemical analysis revealed a checkered pattern with alternating positive broadened or almost absent filaggrin expression. However, no association was found for the two variants of filaggrin (FLG). We conclude that despite a markedly altered filaggrin expression in psoriatic skin, loss-of-function variants of the FLG gene are neither associated with psoriasis vulgaris nor with psoriatic arthritis. The abnormal staining might reflect the altered epidermal differentiation. Our findings imply that the genetic background underlying the epidermal barrier defect in psoriasis is distinct from that found in atopic dermatitis.
authors.affiliation: Institute of Human Genetics, University Erlangen-Nuremberg, Erlangen, Germany. uhueffm@humgenet.uni-erlangen.de
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hüffmeier
authors.forename: Heiko
authors.initials: H
authors.lastname: Traupe
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Oji
authors.forename: Jesús
authors.initials: J
authors.lastname: Lascorz
authors.forename: Markward
authors.initials: M
authors.lastname: Ständer
authors.forename: Jörg
authors.initials: J
authors.lastname: Lohmann
authors.forename: Jörg
authors.initials: J
authors.lastname: Wendler
authors.forename: Harald
authors.initials: H
authors.lastname: Burkhardt
authors.forename: André
authors.initials: A
authors.lastname: Reis
mesh_terms: D015535:Arthritis, Psoriatic / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D000091344:Filaggrin Proteins; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011565:Psoriasis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins