title: Loss-of-function mutations in the filaggrin gene and alopecia areata: strong risk factor for a severe course of disease in patients comorbid for atopic disease.
abstract: Alopecia areata (AA) is a common dermatological disease, which affects nearly 2% of the general population. Association of AA with atopic disease has been repeatedly reported. Loss-of-function mutations in the filaggrin gene (FLG) may be considered as promising candidates in AA, as they have been observed to be a strong risk factor in atopic dermatitis. The FLG mutations R501X and 2282del4 were genotyped in a large sample of AA patients (n=449) and controls (n=473). Although no significant association was observed in the patient sample overall, FLG mutations were significantly associated with the presence of atopic dermatitis among AA patients. Furthermore, the presence of FLG mutations had a strong impact on the clinical course of AA in comorbid patients. For example, 19 of the 22 mutation carriers among AA patients with atopic dermatitis showed a severe form of the disease (P=0.003; odds ratio (OR)=5.47 (95% confidence interval (CI): 1.59-18.76)). In conclusion, our data suggest that when AA occurs in conjunction with FLG-associated atopic disorder, the clinical presentation of AA may be more severe.
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany. regina.betz@uni-bonn.de
authors.forename: Regina C
authors.initials: RC
authors.lastname: Betz
authors.forename: Jana
authors.initials: J
authors.lastname: Pforr
authors.forename: Antonia
authors.initials: A
authors.lastname: Flaquer
authors.forename: Silke
authors.initials: S
authors.lastname: Redler
authors.forename: Sandra
authors.initials: S
authors.lastname: Hanneken
authors.forename: Sibylle
authors.initials: S
authors.lastname: Eigelshoven
authors.forename: Anne-Katrin
authors.initials: AK
authors.lastname: Kortüm
authors.forename: Thomas
authors.initials: T
authors.lastname: Tüting
authors.forename: Julien
authors.initials: J
authors.lastname: Lambert
authors.forename: Jozef
authors.initials: J
authors.lastname: De Weert
authors.forename: Axel M
authors.initials: AM
authors.lastname: Hillmer
authors.forename: Christine
authors.initials: C
authors.lastname: Schmael
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wienker
authors.forename: Roland
authors.initials: R
authors.lastname: Kruse
authors.forename: Gerhard
authors.initials: G
authors.lastname: Lutz
authors.forename: Bettina
authors.initials: B
authors.lastname: Blaumeiser
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000506:Alopecia Areata / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins