Filaggrin loss-of-function variants are associated with atopic dermatitis phenotypes in a diverse, early-life prospective cohort.

Autor: Virolainen SJ; Division of Human Genetics and.; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.; Immunology Graduate Program and.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Satish L; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.; Division of Asthma Research, Cincinnati Children's Hospital, Cincinnati, Ohio, USA., Biagini JM; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.; Division of Asthma Research, Cincinnati Children's Hospital, Cincinnati, Ohio, USA., Chaib H; Division of Human Genetics and.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Chang WC; Division of Asthma Research, Cincinnati Children's Hospital, Cincinnati, Ohio, USA., Dexheimer PJ; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA., Dixon MR; Division of Human Genetics and., Dunn K; Division of Human Genetics and.; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA., Fletcher D; Division of Human Genetics and., Forney C; Division of Human Genetics and.; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA., Granitto M; Division of Human Genetics and.; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA., Hestand MS; Pacific Biosciences, Menlo Park, California, USA., Hurd M; Division of Asthma Research, Cincinnati Children's Hospital, Cincinnati, Ohio, USA., Kauffman K; Division of Human Genetics and.; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Lawson L; Division of Human Genetics and.; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA., Martin LJ; Division of Human Genetics and.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Peña LD; Division of Human Genetics and.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Phelan KJ; Division of Asthma Research, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.; Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Shook M; Division of Human Genetics and.; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA., Weirauch MT; Division of Human Genetics and.; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.; Immunology Graduate Program and.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.; Divisions of Developmental Biology and Bioinformatics and Allergy and Immunology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA., Khurana Hershey GK; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.; Division of Asthma Research, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.; Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Kottyan LC; Division of Human Genetics and.; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.; Immunology Graduate Program and.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.; Divisions of Developmental Biology and Bioinformatics and Allergy and Immunology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2024 Apr 02; Vol. 9 (9). Date of Electronic Publication: 2024 Apr 02.
DOI: 10.1172/jci.insight.178258
Abstrakt: 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.
Databáze: MEDLINE