Prevalence of Filaggrin Gene Mutations: An Evolutionary Perspective

Abstract

The prevalence of filaggrin gene (FLG) mutations varies between different populations. The initial association studies revealed that FLG mutations were causative of ichthyosis vulgaris and strongly associated with atopic dermatitis (AD) in patients of Irish, Scottish, and Danish descent. However, early prevalence data from additional populations indicated that subjects from a North African population lacked the most common FLG mutations (R501X, 2282del4) found in the European populations and were rare or absent in Asian populations. Since then, a high prevalence of FLG loss-of-function variants in the general population and a strong association to disease have been detected. All associated variants have in common that they are either nonsense or frameshift in a coding exon, leading to a loss of filaggrin expression. A high prevalence of FLG mutations is evident in Northern Europe, North America, and parts of Asia. However, the prevalence and association to AD and IV seem low in populations studied from Mediterranean or African countries; also, the prevalence of FLG mutations seems to be lower in Americans of African compared to people of European descent. The prevalence in many other populations, such as those in South America or Oceania, remains to be elucidated. Interestingly, although FLG mutations are prevalent and associated with disease in several Asian populations, the specific loss-of-function variants within the FLG gene vary from those prevalent in Europe and North America. Altogether, FLG displays a remarkable variation in both the type of loss-of-function variants and mutation prevalence between different global populations. Seemingly, there is a north-south gradient of association of those studied to date. The explanation for and significance of these variations may involve an evolutionary role of carrying FLG mutations and will be further discussed.