Hair keratin mutations in tooth enamel increase dental decay risk
Hair keratin mutations in tooth enamel increase dental decay risk
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DOI：
10.1172/jci78272
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发表时间：
2014-12-01
影响因子：
15.9
通讯作者：
Morasso, Maria I.
中科院分区：
文献类型：
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作者：
Duverger, Olivier;Ohara, Takahiro;Morasso, Maria I.
牙釉质是人体中最坚硬的物质，具有独特的硬度和断裂韧性，可保护牙齿免受龋齿，这是全球最常见的慢性疾病。除了高矿物质含量外，牙釉质还包含对机械性能很重要并影响龋齿的发生和发展的有机材料;然而，牙釉质的蛋白质组成尚未完全表征。在这里，我们确定，上皮头发角蛋白，这是至关重要的保持鞘的完整性，支持毛干，表达在釉质器官和成熟的釉质的基本有机成分。使用来自386名儿童和706名成人的遗传和口内检查数据，我们发现在编码角蛋白75（KRT 75），KRT 75（A161 T）和KRT 75（E337 K）的基因中具有已知毛发疾病相关多态性的个体易于增加龋齿。对携带KRT 75（A161 T）变体的个体的牙齿进行分析，发现釉质结构发生改变，釉质硬度显著降低，这表明功能性角蛋白网络是牙齿釉质机械稳定性所必需的。总之，我们的研究结果确定了一个影响釉质结构的遗传位点，并建立了毛发疾病和龋齿易感性之间的联系。
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), KRT75(A161T) and KRT75(E337K), are prone to increased dental caries. Analysis of teeth from individuals carrying the KRT75(A161T) 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.