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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

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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 2

Effects of polymorphism in KRT75 on enamel and tufts structure and on enamel hardness.

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Effects of polymorphism in KRT75 on enamel and tufts structure and on en...
(A) Scanning electron microscopy analysis of ground, polished, and etched human molars from patients with (KRT75GA) or without (KRT75GG) a missense A allele at rs2232387. Asterisk, rod; arrow, interrod. Scale bar: 20 μm. (B) Differential interference contrast imaging of tufts isolated from molars from individuals with KRT75GG or KRT75GA genotype. Scale bar: 500 μm. (C) Detection of KRT75 protein in tufts from individuals with KRT75GG or KRT75GA genotype. Scale bar: 20 μm. (D) Transmission electron microscopy of organic material isolated after demineralization of enamel from individuals with KRT75GG or KRT75GA genotype. Lower panels show high resolution images of enamel rod sheaths. Scale bars: 10 μm (upper panels); 500 nm (lower panels). (E) Vickers enamel hardness (adjusted for race) measured on molar sections from individuals with KRT75GG, KRT75GA, or KRT75GA genotype. n = 6 (3 of mixed European descent and 3 African-Americans) for each group.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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