FLG LoF Variants are Associated with Atopic Dermatitis in an Early-Life Prospective Cohort

We performed targeted sequencing of the FLG gene in 438 children with physician-diagnosed Atopic Dermatitis (AD), identified Loss-of-Function (LoF) variants, and tested the association of having one or more of these variants (binary composite) variants with AD-associated outcomes. We found that having a LoF variant was associated with moderate-severe AD compared to mild AD, food allergy at the first visit, and higher transepidermal water loss (TEWL) in both lesional and non-lesional skin in these children.]]>
The Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) is the first US-based prospective longitudinal early-life cohort of children with AD who complete annual visits with extensive biospecimen collection that has been previously described in Biagini et al 2020. Recruitment began in December of 2016 and is ongoing. Briefly, children in the greater Cincinnati area (southwest Ohio and northern Kentucky) were identified through public advertising or the medical chart at Cincinnati Children's Hospital Medical Center (CCHMC). The recruitment details, exclusion and inclusion criteria, and biospecimen collection and processing of the MPAACH cohort have been detailed previously in Biagini et al 2020. Eligible children were aged at least 2 years at enrollment, were born after a gestation of at least 36 weeks, and either had a diagnosis of AD, based on the Hanifin and Rajka Criteria for Atopic Dermatitis, or their parents/legal authorized representative indicated a positive response to each of the 3 questions from the Children's Eczema Questionnaire. Exclusions include a comorbid lung condition, dependence on immunosuppression or oral steroids for a medical condition other than asthma, conditions precluding biological sample collection or spirometry, and a bleeding diathesis.This study was approved by the institutional review board at CCHMC under protocol number 2016-5842, and all subjects provided informed consent/parental permission before participation. For the present study, blood collected from 452 participants from various visits was subjected to targeted capture sequencing of the FLG gene. ]]>