title: Filaggrin-2 variation is associated with more persistent atopic dermatitis in African American subjects.
abstract: BACKGROUND
  Atopic dermatitis (AD) is a common skin disease characterized by recurrent episodes of itching. Genetic variation associated with the persistence of AD has not been described for African American subjects.
  
  
  OBJECTIVE
  We sought to evaluate genetic variation of filaggrin-2 (FLG2) in African American subjects with AD.
  
  
  METHODS
  We evaluated a multiyear prospective cohort study of African American children with AD with respect to FLG2 variation based on whole-exome sequencing, followed by a targeted analysis. We ultimately evaluated the association of rs12568784 and rs16833974 with respect to the persistence of AD symptoms over time.
  
  
  RESULTS
  Whole-exome analysis was conducted on 60 subjects, revealing a premature stop codon in exon 3 at S2377X (rs12568784) and X2392S (rs150529054) and a large exon 3 deletion mutation, Q2053del224. On the basis of a priori criteria, we then studied rs12568784, rs16833974 (H1249R), and Q2053del224. We noted that patients with S2377X (odds ratio [OR], 0.44; 95% CI, 0.25-0.46) and H1249R (OR, 0.23; 05% CI, 0.12-0.46) were significantly less likely to be free of symptoms of AD, and Q2053del224 (OR, 0.54; 95% CI, 0.16-1.80) trended toward this outcome. S2377X and H1249R were in high linkage disequilibrium (D' = 0.95).
  
  
  CONCLUSIONS
  In an African American cohort with AD, FLG2 mutations were associated with more persistent AD. This is the first finding of genetic variation of a skin barrier protein in subjects of African ancestry with AD.
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa; Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa. Electronic address: margo@upenn.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Margolis
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Gupta
authors.affiliation: Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Apter
authors.affiliation: DNA Sequencing Facility, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.
authors.forename: Tapan
authors.initials: T
authors.lastname: Ganguly
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.
authors.forename: Ole
authors.initials: O
authors.lastname: Hoffstad
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.
authors.forename: Maryte
authors.initials: M
authors.lastname: Papadopoulos
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Rebbeck
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.
authors.forename: Nandita
authors.initials: N
authors.lastname: Mitra
mesh_terms: D001741:Black or African American / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003876:Dermatitis, Atopic / Q000235:genetics*; D005091:Exons; D005260:Female; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009418:S100 Proteins / Q000235:genetics*
chemical_list: C000717249:FLG protein, human; C000717250:FLG2 protein, human; D000091344:Filaggrin Proteins; D009418:S100 Proteins
keywords: Atopic dermatitis; atopy; epidemiology; filaggrin; genetic epidemiology