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 December 1, 2014; First 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 3

Tubular projections of molar fissures forming thin holes deep into the enamel.

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Tubular projections of molar fissures forming thin holes deep into the e...
(A) Backscattered scanning electron microscopy of polished sections of tooth crowns from individuals with common G alleles (KRT75GG) or with missense A alleles (KRT75AA) at rs2232387. Note for KRT75AA the presence of cracks and holes surrounded by partially demineralized enamel (arrow) and containing particles resembling bacteria (arrowhead). Scale bars: 1 mm (upper left and central panels); 20 μm (upper right panel); 50 μm (lower central panel); 10 μm (lower left and right panels). (B) Micro-CT analysis of molars showing the presence of thin holes going from the enamel surface and extending into the dentin detected in patients with the missense A allele. Scale bars: 5 mm. (C) Micro-CT reconstructions of molar sections showing that the thin holes in molars from individuals with a KRT75GA or KRT75AA genotype are tubular projections of the fissures that run throughout the enamel. Enamel is transparent, while dentin is colored in red, based on density. A thin layer at the surface of the enamel appears red due to the transition between air density and enamel density. Scale bars: 1 mm.