What role does genetics play in eczema?

A family history of atopic diseases — and atopic dermatitis in particular — is the strongest predictor, with twin studies suggesting a very high genetic component.^[1] Most of the genetic causes aren’t well understood, but one of the most likely contributors are gene variants of the filaggrin gene (FLG), which codes for filaggrin, an important structural protein of the epidermis that maintains proper skin barrier function.^[2][3][4] That said, most people with atopic dermatitis don’t have any FLG mutations, and a majority of people with FLG mutations won’t develop atopic dermatitis, so it’s only one part of the picture. Another genetic cause is gene variants of the serine peptidase inhibitor kazal type 5 (SPINK5) gene, which codes for a protein that helps regulate desquamation (peeling/shedding of the outermost layer of skin, which is a normal part of cell turnover but can go awry), preventing excessive breakdown of the stratum corneum (the outermost layer of skin). It also has implications for the skin barrier and skin dryness.^[5]

Besides FLG and SPINK5, some other genes related to atopic dermatitis are also related to immune function and inflammation, namely the cytokines IL-4 and IL-10.^[6][7] Gene variants in TLR2 and TLR4, which are involved in the activation of inflammatory signaling, are also associated with a higher risk.^[8]

Atopic dermatitis is a multifaceted disease with many processes that work together; variations in genes related to skin cell turnover, skin barrier maintenance, and inflammation are all likely to contribute.