Filaggrin loss-of-function variants are associated with atopic dermatitis phenotypes in a diverse, early-life prospective cohort
Year: 2024
Type: article
Study design: Observational Study
Abstract: Loss-of-function (LoF) variants in the filaggrin (FLG) gene are the strongest known genetic risk factor for atopic dermatitis (AD), but the impact of these variants on AD outcomes is poorly understood. We comprehensively identified genetic variants through targeted region sequencing of FLG in children participating in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort. Twenty FLG LoF variants were identified, including 1 novel variant and 9 variants not previously associated with AD. FLG LoF variants were found in the cohort. Among these children, the presence of 1 or more FLG LoF variants was associated with moderate/severe AD compared with those with mild AD. Children with FLG LoF variants had a higher SCORing for Atopic Dermatitis (SCORAD) and higher likelihood of food allergy within the first 2.5 years of life. LoF variants were associated with higher transepidermal water loss (TEWL) in both lesional and nonlesional skin. Collectively, our study identifies established and potentially novel AD-associated FLG LoF variants and associates FLG LoF variants with higher TEWL in lesional and nonlesional skin.
Source: JCI Insight
Authors: Samuel J. Virolainen, Latha Satish, Jocelyn M. Biagini, Hassan Chaib, Wan Chi Chang, Phillip J. Dexheimer, Michael R. Dixon, Katelyn Dunn, David Fletcher, Carmy Forney, Marissa Granitto, Matthew S. Hestand, Makenna Hurd, Kenneth Kauffman, Lucinda Lawson, Lisa J. Martin, Loren D.M. Peña, Kieran J. Phelan, Molly Shook, Matthew T. Weirauch, Gurjit K. Khurana Hershey, Leah C. Kottyan
Language: English
Subfield: Dermatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Funders: National Institutes of Health, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G2191075298, G2234417830, G241973223, G244238509, G2542962027, G264301746, Virus-driven human gene misregulation in disease, Role of TET1 in airway epithelium and childhood asthma, G566358457, Genomics of Inflammatory Bowel Disease, G7396908598, G745487158, G9000029701, G9000034084, G9000042482, G9000055200, G9000074399, G9000082378, G9000112267, G9000116733, G9000159478, G9000169229, G9000185946, G9000199090, G9000280622, G9000309704, Cincinnati Rheumatic Diseases Resource Center, Molecular Mechanisms of the Dysregulated Immune Response to Ebola Virus
OpenAlex ID: W4393549299