Effect of filaggrin loss-of-function mutations on atopic dermatitis in young age: a longitudinal birth cohort study

Atopic dermatitis (AD) is a chronic inflammatory skin disease, and skin barrier defects are often observed in patients with AD. So far, few association studies between FLG loss-of-function mutations and onset of AD in longitudinal studies of early childhood have been reported. In the present study, we aimed to investigate the effect of FLG loss-of-function mutations on the development of AD in a longitudinal birth cohort study. The status of AD diagnosis at each age until 6 years was collected from the Tokyo Children's Health, Illness, and Development (T-CHILD) study. We analyzed eight loss-of-function mutations in FLG in 712 participants. FLG loss-of-function mutations were significantly associated with AD onset in infancy (≤2 years) (P < 0.001, OR 3.54, 95% CI 1.88-6.65), but not with AD onset in childhood (≥3 years) (P = 0.981, OR 0.99, 95% CI 0.29-3.36), and none of the children in the present cohort who developed AD at 5 years of age or later carried FLG loss-of-function mutations. Our data support the notion that the effect of FLG loss-of-function mutations is prominent during a very early stage of life.