Hair keratin mutations in tooth enamel increase dental decay risk

Abstract

B r i e f r e p o r t5hair in the facial area upon shaving, is associated with a polymorphism (rs2232387) in the KRT75 gene and more prevalent in AfricanAmericans due to the curly nature of their hair (23). This G-to-A missense mutation (KRT75 GA or KRT75 AA genotypes) leads to an alanine-to-threonine substitution at position 161 (A161T) in a highly conserved region of the 1A α-helical segment of KRT75 ( Figure 1E). To determine whether the KRT75 A161T mutation had clinical impact on enamel function, we tested the genetic association between the KRT75 polymorphism (rs2232387) and tooth decay assessed as dental caries experience in the primary dentition of 386 children (mixed European descent, 6-12 years) and permanent dentition of 706 adults (mixed European descent, 25-50 years). The missense A allele of rs2232387, which was observed in 23% of the samples, was associated with a higher number of carious tooth surfaces in adults but not children ( Figure 1F and Supplemental Table 1).We investigated the expression pattern of KRT75 in mouse enamel organ and in mature human enamel. KRT75 was expressed by mouse ameloblasts at the secretory stage (Supplemental Figure 2A) and detected in the tufts and rod sheaths of mature human enamel ( Figure 1, B and C). Interestingly, until enamel matrix proteins were identified, enamel was thought to be a keratinized structure, like hair and nail, with an extreme degree of mineralization (18,19). Here, we show that a subset of hair keratins is expressed by ameloblasts, and we demonstrate that KRT75 is incorporated into the tufts and rod sheaths in mature enamel. Since keratins are not secreted proteins, their deposition in enamel may be related to the retention of cell fragments at the periphery of the rods (20).Mutations in hair keratins have been reported in various human pathological conditions (21, 22). Among them, pseudofolliculitis barbae, a hair disorder characterized by the formation of ingrown (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. etched tooth samples sectioned in the plane transecting the enamel rods revealed that the distribution and characteristic keyhole shape of the rods were altered in individuals carrying the variant A allele (Figure 2A). Tufts and rod sheaths isolated from patients with the KRT75 GA or KRT75 AA genotype appeared disorganized ( Figure 2B), and the distribution pattern of KRT75 was highly disrupted ( Figure 2C). This was further corroborated by transmission electron microscopy analysis ( Figure 2D). These results suggest that epithelial hair keratins s...

Single Nucleotide Polymorphism in the Aetiology of Caries: Systematic Literature Review

“…Some papers focused on SNP in 1 gene, others on SNPs in several genes. In the majority of the quoted researches caries was evaluated using the DMFT/DMFS index for permanent dentition and the dmft/dmfs index for primary dentition, excepting Duverger et al [2014] (caries presence/absence), Fine et al [2013] (X-ray evaluation), and Fushan et al [2009] (no caries evaluation). The age range of the patients was from 1 to 84 years (9 studies considered children, 9 adults, and 11 both children and adults).…”

“…Authors of some studies included in the review observed the SNP phenomenon in genes involved in amelogenesis [Slayton et al, 2005;Deeley et al, 2008;Patir et al, 2008Kang et al, 2011;Olszowski et al, 2012;Shimizu et al, 2012;Tannure et al, 2012a, b;Wang et al, 2012b;Gasse et al, 2013;Chaussain et al, 2014;Duverger et al 2014;Abbasoğlu et al, 2015;Anjomshoaa et al, 2015;Shaffer et al, 2015;Yildiz et al, 2016]. Amelogenesis is a genetically controlled process of enamel development.…”

Des kératines du cheveu dans l’émail dentaire

“…Ces deux symptomatologies démontrent clairement la fonction cruciale de la kératine 75 dans la gaine de soutien entourant le poil, assurant son guidage au cours de sa croissance ainsi que son ancrage dans la peau. Grâce à une collaboration avec les départements de génétique et d'odontologie de l'université de Pittsburgh (Pennsylvanie, États-Unis), permettant d'associer données génétiques et examens intra-oraux dans une large population d'adultes et d'enfants, nous avons montré que ces deux polymorphismes dans la kératine 75 étaient également associés à un risque plus élevé de développer des caries dentaires [3]. aussi des facteurs génétiques affectant la structure de l'émail ou la composition de la salive [10].…”

“…Le développement des caries fait intervenir de nombreux facteurs tels que l'alimentation, le mode de vie, l'hygiène, mais Fonction des kératines du poil dans l'émail dentaire En analysant de près l'émail de patients porteurs du polymorphisme associé à la pseudo folliculite de la barbe, nous avons démontré que la mutation dans la kératine 75 rend la gaine des prismes de l'émail instable, affecte l'arrangement des prismes, est associée à une réduction de la dureté de la couche interne de l'émail, et favorise la formation de lésions carieuses tubulaires [3]. De façon similaire à sa fonction dans le follicule pileux, la kératine 75 semble donc jouer un rôle crucial dans le guidage des prismes de l'émail au cours de leur formation ainsi que dans le maintien de leur cohésion dans l'émail mature.…”

“…Des kératines du poil dans l'émail dentaire Dans une étude récente menée au NIH dans le laboratoire de Maria I. Morasso, nous avons découvert que des kératines exprimées spécifiquement dans le tissu de soutien entourant le poil étaient éga-lement exprimées par l'organe produisant l'émail [3]. D'autre part, nous avons montré que l'une de ces kératines, la kératine 75, est intégrée dans l'émail où elle est localisée au niveau de la gaine des prismes.…”