Association of Locus Xq26.1-27.3 with Erosive Tooth Wear Phenotypes in a Group of Adolescents.

Erosive tooth wear is a multifactorial condition of an increasing prevalence. There is a need for discovering individual genetic predisposition for the development of this condition. Considering that the chromosome X locus was previously shown to be associated with dental caries, the aim of the present study was to look for the association between this locus and erosive tooth wear when dietary habits are considered as a co-factor. Saliva samples, erosive wear experience data, and dietary information from 16- to 18-year-old dental patients (n = 705) were used. Genotyping analyses were performed, and thereafter, analyses considering diet and oral hygiene data, using logistic regression, with the assumption that erosive tooth wear is a complex gene-environment model. Genotypic analyses revealed an association between chromosome X marker rs1324156 and erosive tooth wear phenotype. Logistic regression analysis showed that, in the presence of less common allele of rs12687601 and rs1324156, erosive tooth wear more likely develops when associated with numerous dietary variables from the questionnaire. These results indicate that erosive tooth wear may be the result of gene-environment interactions.

Genetic variants in pachyonychia congenita-associated keratins increase susceptibility to tooth decay.

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.

Aquaporins' Influence on Different Dental Erosive Wear Phenotypes in Humans.

Dental erosive wear is a multifactorial condition of high prevalence. Nowadays, there is an emphasis on discovering individual genetic predisposition for the development of this condition. Aquaporins (AQPs) are water channel proteins expressed in salivary glands, as well as during tooth development. They are involved in salivary secretion and composition and linked to physiological protection of the oral cavity. The aim of this study was to explore the relationship between different dental erosive wear phenotypes, AQP genes, and selected environmental factors. Data from 705 dental patients were used to investigate the association between dental erosive wear phenotypes and AQPs' single-nucleotide variants. Phenotypes were further analyzed considering diet and oral hygiene data, using logistic regression analysis, as implemented in PLINK, with the assumption that dental erosive wear is a complex gene-environment model. Associations were found between severe erosive tooth wear and rs2878771 (AQP2) for the genotypic (p = 0.02) and dominant (p = 0.03) models, and rs3736309 (AQP5) for the allelic model (p = 0.02). Logistic regression analyses, after implementing the Bonferroni correction, showed that several significant associations were present when covariates were included, suggesting that a strong environmental component is present. Our results show that dental erosive wear establishes under a gene-environmental complex model.

Genome-Wide Association Study of Erosive Tooth Wear in a Finnish Cohort.

Erosive tooth wear is defined as irreversible loss of dental tissues due to intrinsic or extrinsic acids, exacerbated by mechanical forces. Recent studies have suggested a higher prevalence of erosive tooth wear in males, as well as a genetic contribution to susceptibility to erosive tooth wear. Our aim was to examine erosive tooth wear by performing a genome-wide association study (GWAS) in a sample of the Northern Finland Birth Cohort 1966 (n = 1,962). Erosive tooth wear was assessed clinically using the basic erosive wear examination. A GWAS was performed for the whole sample as well as separately for males and females. We identified one genome-wide significant signal (rs11681214) in the GWAS of the whole sample near the genes PXDN and MYT1L. When the sample was stratified by sex, the strongest genome-wide significant signals were observed in or near the genes FGFR1, C8orf86, CDH4, SCD5, F2R, and ING1. Additionally, multiple suggestive association signals were detected in all GWASs performed. Many of the signals were in or near the genes putatively related to oral environment or tooth development, and some were near the regions considered to be associated with dental caries, such as 2p24, 4q21, and 13q33. Replications of these associations in other samples, as well as experimental studies to determine the biological functions of associated genetic variants, are needed.

Genetic variation may explain why females are less susceptible to dental erosion.

Not all individuals at risk for dental erosion (DE) display erosive lesions. The prevalence of DE is higher among male subjects. The occurrence of DE may depend on more than just acidic challenge, with genetics possibly playing a role. The aim of this study was to investigate the association of enamel-formation genes with DE. One premolar and a saliva sample were collected from 90 individuals. Prepared teeth were immersed in 0.01 M HCl (pH 2.2), and enamel loss (µm) was measured using white light interferometry. DNA was extracted from saliva, and 15 single-nucleotide polymorphisms were analysed. Allele and genotype frequencies were related to the enamel loss of the specimens. Single-marker and haplotype analyses were performed using sex as a covariate. Mean enamel loss was higher for male donors than for female donors (P = 0.047). Significant associations were found between enamel loss and amelogenin, X-linked (AMELX), tuftelin 1 (TUFT1), and tuftelin-interacting protein 11 (TFIP11). Analyses showed significant associations between variation in enamel-formation genes and a lower susceptibility to DE in female subjects. The results indicate that susceptibility to DE is influenced by genetic variation, and may, in part, explain why some individuals are more susceptible than others to DE, including differences between female subjects and male subjects.

Enamel formation genes associated with dental erosive wear.

Dental erosive wear is a multifactorial condition that is greatly affected by environmental factors. So far, no study has investigated how dental erosive wear is influenced by variations in enamel formation genes. The aim of the present study was to investigate polymorphisms in genes involved in enamel formation and their influence on enamel susceptibility to dental erosion. DNA samples were collected from 795 Norwegian adolescents aged 16-18 years. Five single-nucleotide polymorphism markers were genotyped in selected candidate genes (ameloblastin, amelogenin, enamelin, tuftelin 1 and tuftelin interacting protein 11), reported to influence enamel formation. Allele and genotype frequencies were compared within two patient groups with dental erosions; all participants with dental erosion and only those with severe dental erosion (erosion extending into dentine). Overrepresentation of the G allele of the enamelin marker was seen in the erosion group compared to the unaffected group (p = 0.047). When erosion severity was considered, statistical significant difference in allele frequency was observed for amelogenin, with the C allele suggesting a protective role (p = 0.02). A suggestive overrepresentation of the TT genotype of the amelogenin marker was also seen in cases with severe erosion (p = 0.049) when compared to cases with no dentine erosion. Amelogenin was also associated with severe erosion in the recessive model; the TT genotype was significantly more frequent in the affected group than in the unaffected group (p = 0.01). The present study suggests that polymorphisms in enamel formation genes are statistically associated with an individual's susceptibility to dental erosive wear.

Genes Involved in Enamel Formation and Their Impact on Caries Susceptibility and Erosive Tooth Wear.

The formation of the dental enamel is a consequence of a complex series of events and when disturbed, visible consequences ranging from hypoplasia to hypomineralization occur. Less dramatic alterations of the enamel structure and conformation are argued to modulate individual susceptibility to dental caries or erosive tooth wear. The effort to associate genes known to regulate dental enamel formation with dental caries experience has been carefully reviewed in the literature, and this chapter reflects on these studies from their conception standpoint, highlighting limitations in design, and adds a review to the work on erosive tooth wear.

Genes and Dietary Preferences and Their Impact on Caries Susceptibility and Erosive Tooth Wear.

A dietary pattern rich in refined sugars is associated with higher caries experience. However, people show differences in references for certain foods, and these differences are genetic in origin. In this chapter, dietary preference is the focus of the discussion of individual susceptibility to dental caries and erosive tooth wear.

Genes Influencing Behavior and Their Impact on Caries Susceptibility and Erosive Tooth Wear.

Behavioral change is one of the proposed interventions to address concerns regarding dental caries and erosive tooth wear. The impact of these interventions, however, is difficult to measure, and they are rarely considered in clinical studies. This chapter briefly discusses behavior having a genetic origin and describes several pathways that should be targeted for future studies.

Genes Involved in Saliva Formation and Composition and Their Impact on Caries Susceptibility and Erosive Tooth Wear.

Saliva interfaces with all oral tissues and modulates the development of dental caries or erosive tooth wear. Its mechanical function of coating all surfaces combined with the components in saliva modulates individual susceptibility to dental caries or erosive tooth wear. The effort to associate genes known to regulate saliva roles with dental caries experience has been carefully reviewed in the literature, and this chapter reflects on these studies from their conception standpoint, highlighting limitations in design, and adds a review to the work on erosive tooth wear.

A controlled study of dental erosion in 2- to 4-year-old twins.

BACKGROUND: Dental erosion (DE) in children is a significant oral health issue and has become a focus for research in clinical paediatric dentistry. AIM: This study investigated DE in the primary dentition of 2- to 4-year-old twin and singleton children with regard to the genetic, medical and dietary factors associated with the condition. DESIGN: The 128 subjects consisted of 88 twin children (31 monozygous, 50 dizygous, 7 unknown zygosity) and singletons (n = 40) aged 2-4 years. Medical, dental, and dietary histories were obtained. The children were examined for DE using a modified index. RESULTS: The prevalence of DE by subject affected was 77% in monozygotic twins (MZ), 74% in dizygotic twins (DZ), and 75% in singleton controls (P > 0.1). Of the teeth scored, 12% had mild, 10% moderate, and 1% severe lesions, and DE was more severe in the older age group (P < 0.05). Concordance rates for erosion lesions in MZ and DZ co-twins were not statistically significant. CONCLUSIONS: The prevalence of DE and the concordance of erosion lesions were similar between MZ and DZ twins and singleton children, suggesting that the contribution of genetic factors to DE is negligible.

Genetic variation may explain why females are less susceptible to dental erosion.

No association between enamel-formation genes and enamel loss (erosion), but there were associations when analysing 'extreme values' for these factors.

Diagnosis and management of toothwear in two children in the same family: a case report.

The incidence of toothwear would appear to be on the increase in children. The main aetiological factor seems to be the increasing consumption of acidic drinks. This paper reports on a sister and brother with erosion whose parents were reluctant to accept that drinking fruit juice through a straw could have resulted in the damage their children's teeth sustained.