Several genes and environmental factors are implicated but the one gene having the biggest role is filaggrin. This gene will be studied here
Synthesis process of filaggrin (flg):
genetic localisation: chromosome 1=epidermal differentiation complex (group of genes coding proteins which are important for the differentiation of the epidermis (keratinocytes). The localisation of the mutation of the filaggrin gene is the same as that of ichthyosis vulgaris in Europeans (not in Asians).
profilaggrin in granular layer (SG) and through differentiation is cleaved in filaggrin peptides
flg is biologically active in that it probably enables aggregation of keratin filaments
It is then released and broken in amino acids=natural moisturising factor (NMF)
The mutation of flg is a strong risk factor for AD: odds ratio of 3 (3 times increased risk). Some elements suggesting an implication of filaggrin on epidermal function are:
- -natural moisturising factor is reduced (decrease stratum corneum hydration)
- -ceramide is not decreased
- -increased TEWL (trans epidermal water loss)
- -increase in skin pH
- -barrier permeability abnormalities
- -flg is also implicated in other conditions other than AD (and Ichthyosis Vulgaris): contact dermatitis to nickel (with or without ear piercing), nickel sensitization, chronic irritant contact dermatitis
Source of information: Weidinger S. Molecular Genetics of Atopic Eczema. 19th Congress of the European Academy of Dermatology and Venereology (EADV) – Gothenburg (Göteborg), Sweden (Sverige).