دورية أكاديمية
Association of Filaggrin Loss-of-Function Variants With Race in Children With Atopic Dermatitis.
| العنوان: | Association of Filaggrin Loss-of-Function Variants With Race in Children With Atopic Dermatitis. |
|---|---|
| المؤلفون: | Margolis DJ; Perelman School of Medicine, University of Pennsylvania, Philadelphia.; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia.; Department of Dermatology, University of Pennsylvania, Philadelphia., Mitra N; Perelman School of Medicine, University of Pennsylvania, Philadelphia.; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia., Wubbenhorst B; Perelman School of Medicine, University of Pennsylvania, Philadelphia.; Division of Translational Medicine and Human Genetics, Department of Medicine, University of Pennsylvania, Philadelphia., D'Andrea K; Perelman School of Medicine, University of Pennsylvania, Philadelphia.; Division of Translational Medicine and Human Genetics, Department of Medicine, University of Pennsylvania, Philadelphia., Kraya AA; Perelman School of Medicine, University of Pennsylvania, Philadelphia.; Division of Translational Medicine and Human Genetics, Department of Medicine, University of Pennsylvania, Philadelphia., Hoffstad O; Perelman School of Medicine, University of Pennsylvania, Philadelphia.; Department of Dermatology, University of Pennsylvania, Philadelphia., Shah S; Perelman School of Medicine, University of Pennsylvania, Philadelphia.; Department of Dermatology, University of Pennsylvania, Philadelphia., Nathanson KL; Perelman School of Medicine, University of Pennsylvania, Philadelphia.; Division of Translational Medicine and Human Genetics, Department of Medicine, University of Pennsylvania, Philadelphia.; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia. |
| المصدر: | JAMA dermatology [JAMA Dermatol] 2019 Nov 01; Vol. 155 (11), pp. 1269-1276. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Medical Association Country of Publication: United States NLM ID: 101589530 Publication Model: Print Cited Medium: Internet ISSN: 2168-6084 (Electronic) Linking ISSN: 21686068 NLM ISO Abbreviation: JAMA Dermatol Subsets: PubMed not MEDLINE; MEDLINE |
| أسماء مطبوعة: | Original Publication: Chicago, IL : American Medical Association, [2013]- |
| مستخلص: | Importance: Atopic dermatitis (AD) is a common chronic illness that has been associated with variation in the filaggrin gene (FLG). Four variants are most often evaluated. Objectives: To comprehensively describe and compare results from targeted sequencing of FLG loss-of-function (LoF) variants in children of African and European ancestry and the association of these variants with onset and persistence of AD. Design, Setting, and Participants: This prospective US cohort study assessed the genetic subcohort of the Pediatric Eczema Elective Registry (PEER). Children with mild to moderate AD were included in the analysis. Massively parallel sequencing (MPS) was used to focus on FLG LoF variation in white and African American children. Patients were enrolled from June 2005 through July 2017. Data were analyzed from January 25 through May 10, 2019. Main Outcomes and Measures: Associations of FLG LoF variation with white and African American ancestry and with the risk and persistence of AD. Results: A total of 741 children were included in the analysis (394 [53.2%] female and 347 [46.8%] male; mean [SD] age at onset, 1.97 [2.72] years); of these, 394 (53.2%) were white, 326 (44.0%) were African American, and 21 (2.8%) were of other ancestries. Using MPS technology, 23 FLG LoF variants were found in children with AD. The prevalence of FLG LoF variants was 177 participants (23.9%) in the full cohort, 124 white participants (31.5%), and 50 African American participants (15.3%). The odds ratio for carrying any FLG LoF variant in a white child compared with an African American child with AD was 2.44 (95% CI, 1.76-3.39). Some FLG LoF variants are only found in children of a specific ancestry (eg, p.S3316* and p.R826* were not seen in white patients). Children with an FLG LoF were more likely to have persistent AD (odds ratio, 0.67; 95% CI, 0.56-0.80). Conclusions and Relevance: The FLG LoF variants in a US cohort of children with mild to moderate AD differ significantly by race and their association with the persistence of AD. Conventional testing of the 4 frequently evaluated variants is inadequate. Any planned genetic diagnostic test for AD based on FLG LoF variants must be inclusive and not rely on the most frequently studied variants. |
| معلومات مُعتمدة: | R01 AR069062 United States AR NIAMS NIH HHS |
| تواريخ الأحداث: | Date Created: 20190801 Latest Revision: 20220422 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6669787 |
| DOI: | 10.1001/jamadermatol.2019.1946 |
| PMID: | 31365035 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2168-6084 |
|---|---|
| DOI: | 10.1001/jamadermatol.2019.1946 |