Maternal Filaggrin Mutations Increase the Risk of Atopic Dermatitis in Children: An Effect Independent of Mutation Inheritance

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Most human diseases are caused by a combination of multiple environmental and genetic influences. The widely used case/control approach aims to identify disease risk genes by comparing the genetic constitution of affected and healthy individuals. Although successful, this approach ignores additional mechanisms influencing disease risk. Here, we studied mutations in the filaggrin gene (FLG), which are strong risk factors for atopic dermatitis (AD) and allergies, in a large number of families with AD. We found that FLG mutations in the mother, not the father, increased the AD risk of the children, even if the child did not inherit the mutation. Thus, our study revealed, for the first time, a direct influence of a maternal mutation on the child’s risk for a common disease. The maternal FLG effect was only found when the mothers were allergic, and was absent in families of non-allergic mothers. This finding suggests that FLG-induced changes in the maternal immune response shape the child’s immune system during pregnancy and increase the child’s risk for AD. Our study indicates that maternal FLG mutations act as strong environmental risk factors for the child and highlights the potential of family-based studies in uncovering novel disease mechanisms in medical genetics.

Vyšlo v časopise: Maternal Filaggrin Mutations Increase the Risk of Atopic Dermatitis in Children: An Effect Independent of Mutation Inheritance. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005076
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005076

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