Genetic/Protein Association of Atopic Dermatitis and Tooth Agenesis

Abstract

Atopic dermatitis and abnormalities in tooth development (including hypomineralization, hypodontia and microdontia) have been observed to co-occur in some patients. A common pathogenesis pathway that involves genes and protein interactions has been hypothesized. This review aims to first provide a description of the key gene mutations and signaling pathways associated with atopic dermatitis and tooth agenesis (i.e., the absence of teeth due to developmental failure) and identify the possible association between the two diseases. Second, utilizing a list of genes most commonly associated with the two diseases, we conducted a protein-protein network interaction analysis using the STRING database and identified a novel association between the Wnt/β-catenin signaling pathway (major pathway responsible for TA) and desmosomal proteins (component of skin barrier that affect the pathogenesis of AD). Further investigation into the mechanisms that may drive their co-occurrence and underlie the development of the two diseases is warranted.

Keywords: atopic dermatitis; gene–protein interaction; skin barrier; tooth agenesis.

Figure 1

Defective epidermal barrier in atopic dermatitis (AD). The genes that affect SC may have an effect on both corneocytes and CE. For example, the filaggrin protein can be found in corneocytes but it aggregates keratin, affecting the whole SC. Therefore, genes with specific localization of action are placed in the small boxes, while the others are placed in the larger box of SC.

Figure 2

Schematic representation of tooth development stages. (Modified from the work of Nanci A. in 2013. Development of the tooth and its supporting tissues [59]) Main groups of signaling pathways and genes associated with tooth agenesis (TA). Gene mutations in Wnt pathway (orange box), TGF--β/BMP pathway (blue box), EDA/EDAR/κB pathway (green box) and SPARC family (purple box) affecting the initiation stage of tooth development results in tooth agenesis.

Figure 3

Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis reveals protein interaction networks between tooth agenesis and atopic dermatitis proteins. The color-coded nodes presented proteins, while color-coded lines represent protein–protein associations. Light blue lines represent associations in curated databases; pink lines represent experimentally determined associations derived from experimental/biochemical data; light green lines represent text-mining associations meaning “co-mentioned in PubMed abstracts”; black lines represent co-expression of genes in homo sapiens or other organisms; light purple lines represent putative homologs. There were no predicted interactions (green, red and blue lines) in the results.