Filaggrin-2 variation is associated with more persistent atopic dermatitis in African American subjects - 01/03/14
, Jayanta Gupta, MD, PhD a, ∗, Andrea J. Apter, MD, MSc c, Tapan Ganguly, PhD d, Ole Hoffstad, MA a, Maryte Papadopoulos, MBE a, Tim R. Rebbeck, PhD a, Nandita Mitra, PhD aAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Atopic dermatitis, filaggrin, epidemiology, genetic epidemiology, atopy
Abbreviations used : AD, EDC, FLG, FLG2, LD, MAF, OR, PEER, RPTN, SFTP
Plan
| Supported by R01-AR0056755 from the National Institute of Arthritis Musculoskeletal and Skin Diseases and from a grant from Valeant Pharmaceuticals for the Pediatric Eczema Elective Registry study. |
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| Disclosure of potential conflict of interest: D. J. Margolis has received grants from the National Institutes of Health (NIH) and Valent. A. J. Apter has received grants from the NIH, AstraZeneca, and Bristol-Myers Squibb; is a board member for the American Academy of Allergy, Asthma & Immunology; and has consultant arrangements with UpToDate. T. Ganguly, M. Papadopoulos, and N. Mitra have received a grant from the NIH. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 133 - N° 3
P. 784-789 - mars 2014 Retour au numéro
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