bromochloroacetic-acid and Tooth-Erosion

Pachyonychia congenita (PC) is a cutaneous disorder primarily characterized by nail dystrophy and painful palmoplantar keratoderma. PC is caused by mutations in KRT6A, KRT6B, KRT6C, KRT16, and KRT17, a set of keratin genes expressed in the nail bed, palmoplantar epidermis, oral mucosal epithelium, hair follicle and sweat gland. RNA-seq analysis revealed that all PC-associated keratins (except for Krt6c that does exist in the mouse genome) are expressed in the mouse enamel organ. We further demonstrated that these keratins are produced by ameloblasts and are incorporated into mature human enamel. Using genetic and intraoral examination data from 573 adults and 449 children, we identified several missense polymorphisms in KRT6A, KRT6B and KRT6C that lead to a higher risk for dental caries. Structural analysis of teeth from a PC patient carrying a p.Asn171Lys substitution in keratin-6a (K6a) revealed disruption of enamel rod sheaths resulting in altered rod shape and distribution. Finally, this PC-associated substitution as well as more frequent caries-associated SNPs, found in two of the KRT6 genes, that result in p.Ser143Asn substitution (rs28538343 in KRT6B and rs151117600 in KRT6C), alter the assembly of K6 filaments in ameloblast-like cells. These results identify a new set of keratins involved in tooth enamel formation, distinguish novel susceptibility loci for tooth decay and reveal additional clinical features of pachyonychia congenita.

Topics: Adult; Amino Acid Substitution; Animals; Cells, Cultured; Child; Dental Caries; Dental Enamel; Female; Gene Frequency; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Keratin-6; Keratins; Male; Mice; Middle Aged; Pachyonychia Congenita; Polymorphism, Single Nucleotide; Rats; Tooth Erosion

The use of smokeless tobacco appears to be finding its way onto middle school, high school and college campuses as a socially acceptable and popular habit. Numerous reports in the literature have described the oral changes that appear to be associated with the use of smokeless tobacco in adults. Such information is unavailable for the lower age groups. A study was therefore undertaken to determine the prevalence and frequency of oral hard- and soft-tissue alterations associated with the use of smokeless tobacco in a teen-age population. High school students in grades 9 to 12 were evaluated on a random basis. From a total sample of 1,119 students, 117 users of smokeless tobacco were identified. Four distinct lesions associated with smokeless tobacco use were identified clinically: (1) hyperkeratotic or erythroplakic lesions of the oral mucosa, (2) gingival or periodontal inflammation, (3) a combination of oral mucosal lesions and periodontal inflammation, and (4) cervical erosion of the teeth. Among the smokeless tobacco users, 113 were boys and 4 were girls. Fifty-seven (48.7 percent) of the users had soft-tissue lesions and/or periodontal inflammation or erosion of dental hard tissues. Ninety-nine of the 117 users were Caucasian, 6 were Hispanic, 1 was black, 1 was Asian, 1 was an American Indian, and 6 failed to identify an ethnic origin. Use ranged from one to twenty "dips" per day, with an average time per dip of 30 minutes. Most users had been dipping for an average of 2 years, and twelve different tobacco brands were identified.

Topics: Adolescent; Adult; Female; Gingivitis; Humans; Keratins; Male; Mouth Mucosa; Nicotiana; Periodontitis; Plants, Toxic; Time Factors; Tooth Erosion