Hair keratin mutations in tooth enamel increase dental decay risk
Olivier Duverger, … , Mary L. Marazita, Maria I. Morasso
Olivier Duverger, … , Mary L. Marazita, Maria I. Morasso
Published October 27, 2014
Citation Information: J Clin Invest. 2014;124(12):5219-5224. https://doi.org/10.1172/JCI78272.
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Brief Report Genetics

Hair keratin mutations in tooth enamel increase dental decay risk

Abstract

Tooth enamel is the hardest substance in the human body and has a unique combination of hardness and fracture toughness that protects teeth from dental caries, the most common chronic disease worldwide. In addition to a high mineral content, tooth enamel comprises organic material that is important for mechanical performance and influences the initiation and progression of caries; however, the protein composition of tooth enamel has not been fully characterized. Here, we determined that epithelial hair keratins, which are crucial for maintaining the integrity of the sheaths that support the hair shaft, are expressed in the enamel organ and are essential organic components of mature enamel. Using genetic and intraoral examination data from 386 children and 706 adults, we found that individuals harboring known hair disorder–associated polymorphisms in the gene encoding keratin 75 (KRT75), KRT75A161T and KRT75E337K, are prone to increased dental caries. Analysis of teeth from individuals carrying the KRT75A161T variant revealed an altered enamel structure and a marked reduction of enamel hardness, suggesting that a functional keratin network is required for the mechanical stability of tooth enamel. Taken together, our results identify a genetic locus that influences enamel structure and establish a connection between hair disorders and susceptibility to dental caries.

Authors

Olivier Duverger, Takahiro Ohara, John R. Shaffer, Danielle Donahue, Patricia Zerfas, Andrew Dullnig, Christopher Crecelius, Elia Beniash, Mary L. Marazita, Maria I. Morasso

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Figure 1

Epithelial hair keratins in enamel and association of polymorphism in KRT75 with increased susceptibility to caries in humans.

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Epithelial hair keratins in enamel and association of polymorphism in KR...
(A) Diagram representing the 2 keratin clusters on chromosomes 11q and 15q and highlighting the keratins expressed in mouse enamel organ and those that are downregulated in Dlx3K14-cKO mice at P10 (RNA-seq). (B) Detection of KRT75 on polished and etched section of mature human tooth showing the dentin-enamel junction (DEJ) and cross sections of enamel rods. Magnification on the right shows enamel rods (asterisk) and interrods (arrow). Scale bars: 100 μm (left); 20 μm (right).(C) Isolation of organic material (enamel tufts and rod sheaths) from human enamel (En) after demineralization. Enamel tufts are visualized at the surface of the dentin (De). (D) Detection of KRT75 in isolated organic material. Scale bars: 100 μm; 20 μm (inset). (E) Sequencing of the human KRT75 gene harboring a missense polymorphism (rs2232387, asterisks). Three genotypes are shown: KRT75GG, KRT75GA, and KRT75AA. (F) Genetic association between the rs2232387 polymorphism and caries experience in primary and permanent dentition. Pie charts show allelic distribution of the rs2232387 polymorphism measured on 706 adults and 386 children. Graphs show measure of caries experience for each genotype: left, number of tooth surfaces with untreated decay (DS and ds); center, number of decayed, missing due to decay, and filled surfaces (DMFS and dfs); right, partial DMFS and dfs indices limited to the molars and premolars pit and fissure (PF and pf) surfaces.