title: The Value of FLG Null Mutations in Predicting Treatment Response in Atopic Dermatitis: An Observational Study in Finnish Patients.
abstract: The contribution of filaggrin null mutations to predicting atopic dermatitis (AD) treatment response is not clear, nor have such mutations been studied in the Finnish population. This study tested the association of the 4 most prevalent European FLG null mutations, the 2 Finnish enriched FLG null mutations, the FLG 12-repeat allele, and 50 additional epidermal barrier gene variants, with risk of AD, disease severity, clinical features, risk of other atopic diseases, age of onset, and treatment response in 501 patients with AD and 1,710 controls. AD, early-onset AD, palmar hyperlinearity, and asthma showed significant associations with the combined FLG null genotype. Disease severity and treatment response were independent of patient FLG status. Carrier frequencies of R501X, 2282del4, and S3247X were notably lower in Finns compared with reported frequencies in other populations. This data confirms FLG mutations as risk factors for AD in Finns, but also questions their feasibility as biomarkers in predicting treatment response.
authors.affiliation: Human Genomics, Institute for Molecular Medicine Finland FIMM, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Tiia Maria
authors.initials: TM
authors.lastname: Luukkonen
authors.forename: Ville
authors.initials: V
authors.lastname: Kiiski
authors.forename: Maria
authors.initials: M
authors.lastname: Ahola
authors.forename: Johanna
authors.initials: J
authors.lastname: Mandelin
authors.forename: Hannele
authors.initials: H
authors.lastname: Virtanen
authors.forename: Minna
authors.initials: M
authors.lastname: Pöyhönen
authors.forename: Sirpa
authors.initials: S
authors.lastname: Kivirikko
authors.forename: Ida
authors.initials: I
authors.lastname: Surakka
authors.forename: Sakari
authors.initials: S
authors.lastname: Reitamo
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.forename: Markku
authors.initials: M
authors.lastname: Heliövaara
authors.forename: Eveliina
authors.initials: E
authors.lastname: Jakkula
authors.forename: Anita
authors.initials: A
authors.lastname: Remitz
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003876:Dermatitis, Atopic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D000091344:Filaggrin Proteins; D005387:Finland; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007166:Immunosuppressive Agents; D007381:Intermediate Filament Proteins