Prevalence of Filaggrin Gene Mutations: An Evolutionary Perspective
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 Iri
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Marten C.G. Winge and Maria Bradley
Contents 12.1
Europe ......................................................... 121
12.2
Asia .............................................................. 121
12.3
North America and Africa ........................ 121
12.4
A Possible Evolutionary Role of Carrying FLG Mutations ...................... 123
References ................................................................. 124
M.C.G. Winge, MD, PhD (*) Department of Dermatology, Program in Epithelial Biology, Stanford University, 269 Campus Drive, Stanford, CA 94035, USA e-mail: [email protected] M. Bradley, MD, PhD Department of Dermatology, Institution of Medicine, Karolinska University Hospital, Stockholm, 17176, Sweden e-mail: [email protected]
The impact of filaggrin gene (FLG) mutations seems to have a peculiar pattern on disease, strongly associated with certain diseases (atopic dermatitis (AD) [1], ichthyosis vulgaris (IV) [2]) and having disease-modifying effects in others (i.e., X-linked recessive ichthyosis, pachyonychia congenita) [3–5]. Nevertheless, FLG mutations seem to be prevalent even in the general population. The identification of disease-causing FLG mutations, being either nonsense or frameshift mutations in a protein-coding exon, has enabled identification of causative variants directly from sequence analysis [1, 6]. Due to the close homology between different filaggrin repeats, genotyping has been hampered until a comprehensive sequencing strategy was established [1, 2, 7]. The repetitive nature of the region is reflecting the scarce information currently available in public databases on FLG mutation prevalence data or haplotype-tagging SNPs in general populations. Although this is likely to change, currently FLG mutation prevalence data are mainly derived from individual studies, where either the entire FLG gene has been sequenced or, for the main part, only selected known risk variants tested [8]. Therefore, there is a risk of underestimating the prevalence rates in populations where only certain variants have been tested. Taking that into account, loss-of-function variants have been extensively studied in certain populations such as the UK, Germany, and Japan and are prevalent in the general population, as well as robust risk factors for developing disease. The prevalence of FLG mutations still remains largely unexplored
J.P. Thyssen, H. Maibach (eds.), Filaggrin, DOI 10.1007/978-3-642-54379-1_12, © Springer-Verlag Berlin Heidelberg 2014
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