Filaggrin mutations, atopic eczema, hay fever, and asthma in children

Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk

“…Subsequently an impressive series of replication studies [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] confirmed that these polymorphisms confer an exceptionally strong risk for eczema and subsequent allergen sensitization and that FLG is one of the strongest known genes for complex diseases in general [22][23][24][25] .…”

Atopic conditions other than asthma and risk of the 2009 novel H1N1 infection in children: A case‐control study

“…38,39 Recent studies suggest that mutations in the filaggrin gene are associated with an increased risk of atopic dermatitis, leading to a heritable epithelial barrier defect and diminished epidermal defense mechanisms against microbial organisms, 40 -44 but the mutations increase risk of allergic rhinitis and asthma only in the context of eczema. 43 Filaggrin expression has not been detected in human bronchial epithelial cells but in the anterior vestibulum of the nose. 43 Based on our study findings on the increased risk of H1N1 influenza among patients with atopic dermatitis, filaggrin mutations in the nasal epithelial cells might have an important implication on susceptibility to viral infections.…”

“…43 Filaggrin expression has not been detected in human bronchial epithelial cells but in the anterior vestibulum of the nose. 43 Based on our study findings on the increased risk of H1N1 influenza among patients with atopic dermatitis, filaggrin mutations in the nasal epithelial cells might have an important implication on susceptibility to viral infections. Given the reported increased risk of H1N1 in children with asthma, 19 additional studies are needed to understand the mechanisms underlying the increased risk of H1N1 influenza in the context of the unique alteration in immune functions and airway architecture in atopic individuals.…”

Clinical Impact of Current Genetics Findings

“…Remarkably, FLG null alleles are rather common with carrier frequencies of ~8% in the general population and around 20% in AD cases [61,63,64]. In two large population-based studies [65,66] it was demonstrated that, assuming causality, filaggrin mutations account for up to 15% of the total causality of all AD in these populations. Thus, FLG mutations are the strongest and best replicated genetic risk for AD to date.…”