To evaluate the observed correlation between atopic dermatitis (AD) and tooth agenesis, researchers aimed to provide a description of the key gene mutations and signaling pathways associated with those processes and identify the possible association between the two diseases. They also conducted a protein-protein network interaction analysis using a list of the genes most often correlated with the two diseases.1
Some studies have suggested a link between AD and tooth abnormalities, including dental caries, hypomineralization, and hypodontia. Because skin and teeth have a shared ectodermal tissue origin, an “ectodermal subclinical development defect” has been proposed, suggesting that structural defects in teeth occur because of a common pathogenic pathway as AD.
Tooth agenesis (TA) is an extreme form of abnormality where teeth completely fail to form. TA is comprised of 3 groups, ranging from fewer than 6 missing teeth, 6 or more missing teeth, or a complete absence of teeth. TA is primarily genetic. During embryogenesis, epithelial–mesenchymal interactions have critical roles in signaling molecules and transcription elements.
“The most significant gene variants associated with AD are the loss-of-function mutations found in the filaggrin (FLG) gene. An estimated 27.5% of Caucasian Americans, 48% of Europeans, 31.4% of Chinese and 20% of Japanese populations with AD present mutations in the FLG gene. OVOL1 (ovo-like transcriptional repressor) is an upstream transcription factor that regulates FLG expression.”1 These two genes, FLG and OVOL1, along with IL13, are the 3 genes most commonly found to be associated with development of AD.
Other genes with possible connections to AD include KLK7, SPINK5, LEKTI, SPRR3, among others. Genes involved with vitamin D synthesis and metabolism have also been shown to be related to the development of AD.
Genes related to TA include PAX9, MSX1, AXIN2, DKK1, EDA, and EDA receptor genes, among others. Signaling pathways for tooth development can also be disrupted, causing TA and other tooth abnormalities.
Researchers did not observe any direct overlap between the genes involved in development of AD and TA. However, they suggested that processes or indirect interactions between developmental pathways could be linked. To further examine this possibility, they conducted an investigation of the protein-protein interaction network between TA and AD using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database.
In their analysis, investigators found possible protein-protein interactions (PPI) between proteins involved in AD and TA, particularly between desmosomal proteins and β-catenin. “β-catenin is a key component of the Wnt/β-catenin signaling pathway, which is the major pathway responsible for TA.”1 It is possible that the development of AD and TA occurs through this pathway, although further study is needed.
- Ouyang W, Goh CE, Ng WB, Chew FT, Yap EPH, Hsu C-yS. Genetic/protein association of atopic dermatitis and tooth agenesis. International Journal of Molecular Sciences. 2023; 24(6):5754. https://doi.org/10.3390/ijms24065754