Association between genetic variants in key vitamin‐D‐pathway genes and external apical root resorption linked to orthodontic treatment

This study evaluated the association between single-nucleotide polymorphisms (SNPs) in vitamin-D-related genes and the amount of external apical root resorption linked to orthodontic treatment. One hundred and forty-three individuals were assessed. The amount of external apical root resorption of upper central incisors (EARRinc) and lower first molars (EARRmol) were evaluated in radiographs. Seven SNPs were genotyped across four genes including the vitamin D receptor [VDR], group-specific component [GC], cytochrome P450 family 27 subfamily B member 1 [CYP27B1], and cytochrome P450 family 24 subfamily A member 1 [CYP24A1]. Linear regressions were implemented to determine allele-effects on external apical root resorption. Individuals carrying the AA genotype in VDR rs2228570 had a 21% higher EARRmol than those having AG and GG genotypes (95% CI: 1.03,1.40). EARRmol in heterozygous rs2228570, was 12% lower than for homozygotes (95%CI: 0.78,0.99). Participants with the CCG haplotype (rs1544410-rs7975232-rs731236) in VDR had an EARRmol 16% lower than those who did not carry this haplotype. Regarding CYP27B1 rs4646536, EARRinc in participants who had at least one G allele was 42% lower than for homozygotes AA (95%CI: 0.37,0.93). Although these results did not remain significant after multiple testing adjustment, potential associations may still be suggested. Further replication studies are needed to confirm or refute these findings

Genetic mapping of high caries experience on human chromosome 13

Background: Our previous genome-wide linkage scan mapped five loci for caries experience. The purpose of this study was to fine map one of these loci, the locus 13q31.1, in order to identify genetic contributors to caries.Methods: Seventy-two pedigrees from the Philippines were studied. Caries experience was recorded and DNA was extracted from blood samples obtained from all subjects. Sixty-one single nucleotide polymorphisms (SNPs) in 13q31.1 were genotyped. Association between caries experience and alleles was tested. We also studied 1,481 DNA samples obtained from saliva of subjects from the USA, 918 children from Brazil, and 275 children from Turkey, in order to follow up the results found in the Filipino families. We used the AliBaba2.1 software to determine if the nucleotide changes of the associated SNPs changed the prediction of the presence of transcription-binding site sequences and we also analyzed the gene expression of the genes selected based on binding predictions. Mutation analysis was also performed in 33 Filipino individuals of a segment of 13q31.1 that is highly conserved in mammals.Results: Statistically significant association with high caries experience was found for 11 markers in 13q31.1 in the Filipino families. Haplotype analysis also confirmed these results. In the populations used for follow-up purposes, associations were found between high caries experience and a subset of these markers. Regarding the prediction of the transcription-binding site, the base change of the SNP rs17074565 was found to change the predicted-binding of genes that could be involved in the pathogenesis of caries. When the sequence has the allele C of rs17074565, the potential transcription factors binding the sequence are GR and GATA1. When the subject carries the G allele of rs17074565, the potential transcription factor predicted to bind to the sequence is GATA3. The expression of GR in whole saliva was higher in individuals with low caries experience when compared to individuals with high caries experience (p = 0.046). No mutations were found in the highly conserved sequence.Conclusions: Genetic factors contributing to caries experience may exist in 13q31.1. The rs17074565 is located in an intergenic region and is predicted to disrupt the binding sites of two different transcription factors that might be involved with caries experience. GR expression in saliva may be a biomarker for caries risk and should be further explored. © 2013 Küchler et al.; licensee BioMed Central Ltd

Aquaporin 5 interacts with fluoride and possibly protects against caries

Aquaporins (AQP) are water channel proteins and the genes coding for AQP2, AQP5, and AQP6 are clustered in 12q13. Since AQP5 is expressed in serous acinar cells of salivary glands, we investigated its involvement in caries. DNA samples from 1,383 individuals from six groups were studied. Genotypes of eight single nucleotide polymorphisms covering the aquaporin locus were tested for association with caries experience. Interaction with genes involved in enamel formation was tested. The association between enamel microhardness at baseline, after creation of artificial caries lesion, and after exposure to fluoride and the genetic markers in AQP5 was tested. Finally, AQP5 expression in human whole saliva, after exposure to fluoride in a mammary gland cell line, which is known to express AQP5, and in Wistar rats was also verified. Nominal associations were found between caries experience and markers in the AQP5 locus. Since these associations suggested that AQP5 may be inhibited by levels of fluoride in the drinking water that cause fluorosis, we showed that fluoride levels above optimal levels change AQP5 expression in humans, cell lines, and rats. We have shown that AQP5 is involved in the pathogenesis of caries and likely interacts with fluoride

Role of estrogen related receptor beta (ESRRB) in DFN35B hearing impairment and dental decay

Background: Congenital forms of hearing impairment can be caused by mutations in the estrogen related receptor beta (ESRRB) gene. Our initial linkage studies suggested the ESRRB locus is linked to high caries experience in humans.Methods: We tested for association between the ESRRB locus and dental caries in 1,731 subjects, if ESRRB was expressed in whole saliva, if ESRRB was associated with the microhardness of the dental enamel, and if ESRRB was expressed during enamel development of mice.Results: Two families with recessive ESRRB mutations and DFNB35 hearing impairment showed more extensive dental destruction by caries. Expression levels of ESRRB in whole saliva samples showed differences depending on sex and dental caries experience.Conclusions: The common etiology of dental caries and hearing impairment provides a venue to assist in the identification of individuals at risk to either condition and provides options for the development of new caries prevention strategies, if the associated ESRRB genetic variants are correlated with efficacy. © 2014 Weber et al.; licensee BioMed Central Ltd

Different contribution of BRINP3 gene in chronic periodontitis and peri-implantitis: A cross-sectional study

Background: Peri-implantitis is a chronic inflammation, resulting in loss of supporting bone around implants. Chronic periodontitis is a risk indicator for implant failure. Both diseases have a common etiology regarding inflammatory destructive response. BRINP3 gene is associated with aggressive periodontitis. However, is still unclear if chronic periodontitis and peri-implantitis have the same genetic background. The aim of this work was to investigate the association between BRINP3 genetic variation (rs1342913 and rs1935881) and expression and susceptibility to both diseases. Methods: Periodontal and peri-implant examinations were performed in 215 subjects, divided into: healthy (without chronic periodontitis and peri-implantitis, n = 93); diseased (with chronic periodontitis and peri-implantitis, n = 52); chronic periodontitis only (n = 36), and peri-implantitis only (n = 34). A replication sample of 92 subjects who lost implants and 185 subjects successfully treated with implants were tested. DNA was extracted from buccal cells. Two genetic markers of BRINP3 (rs1342913 and rs1935881) were genotyped using TaqMan chemistry. Chi-square (p<0.05) compared genotype and allele frequency between groups. A subset of subjects (n = 31) had gingival biopsies harvested. The BRINP3 mRNA levels were studied by CT method (2δδCT). Mann-Whitney test correlated the levels of BRINP3 in each group (p<0.05). Results: Statistically significant association between BRINP3 rs1342913 and peri-implantitis was found in both studied groups (p<0.04). The levels of BRINP3 mRNA were significantly higher in diseased subjects compared to healthy individuals (p<0.01). Conclusion: This study provides evidence that the BRINP3 polymorphic variant rs1342913 and low level of BRINP3 expression are associated with peri-implantitis, independently from the presence of chronic periodontitis

Studies of dental anomalies in a large group of school children

The identification of specific patterns of dental anomalies would allow testing the hypothesis that certain genetic and environmental factors contribute to distinct dental anomaly subphenotypes. A sexual dimorphism in tooth agenesis and its association with other dental anomalies has been suggested. The aim of this study was to investigate a large group of children to define dental anomaly subphenotypes that may aid future genetic studies. Orthopantamograms of 1198 subjects were examined and 1167 were used in this study. The frequency of tooth agenesis in the studied population was 4.8%. Male:female ratios varied from 2:1 in the agenesis of upper lateral incisors to 0.5:1 in premolar agenesis. The risk of infra-occlusion of primary molars and double formation of primary incisors was increased in individuals with tooth agenesis. © 2008 Elsevier Ltd. All rights reserved

Caries experience in individuals with cleft lip and palate

Purpose: The purpose of this study was to assess if children with clefts have an increased caries experience. Methods: Caries data was collected via clinical examination of 115 4- to 21-year-olds with clefts and 230 controls. Cleft type was confirmed through their medical records and fluoride exposure history; oral hygiene habits and dietary history were obtained though a questionnaire. Results: The adherence to the preventive oral health habits (toothbrushing, use of fluoride, and dietary factors) were not different among groups excluding the use of dental floss. The mean DMFT was 1.20 (±1.8 SD) for the cleft group and 0.90 (±1.8) for the control group. There was no significant difference in the DMFT scores between children with clefts and the control group (P=.16). The mean dmft was 1.68 (±2.1) for the cleft group and 2.61 (±2.9) for the control group. The prevalence of dental caries in primary teeth was significantly lower in the cleft-affected children vs the control group (P=.02).The percentage of caries-free individuals was similar in cleft and control groups (P=.90), and was also similar in different cleft types (P=.67). Conclusion: Caries experience in children born with clefts is not higher in comparison to control children

Mesio-distal and buccal-lingual tooth dimensions are part of the cleft spectrum: A pilot for future genetic studies

Objective: Considering that oral clefts and tooth dimensions may be part of the same phenotypic spectrum, the aim of this study was to investigate tooth dimensions in permanent dentition and dental malformations, including tooth size discrepancies, of subjects born with clefts compared with individuals without clefts. Design: Cross-sectional study. Participants: The cleft group was composed of 66 subjects, and the noncleft group consisted of 66 healthy unrelated subjects. Main Outcome Measures: The mesio-distal and buccal-lingual crown diameter of fully erupted permanent teeth outside the cleft area was measured using a digital caliber. Clinical records and radiographs were used to evaluate the type of clefts and dental anomalies. Results: The lower second premolar was significantly reduced in the CLP and CP groups. The upper lateral incisor was found to be significantly smaller in the CP group, only for mesio-distal dimensions (P<.05). Dental agenesis was found in eight (12%) cleft subjects and supernumerary teeth in two (3%). Conclusions: Subjects born with oral clefts presented size reduction in specific dental groups. © Copyright 2013 American Cleft Palate-Craniofacial Association

MMP13 polymorphism decreases risk for dental caries

Recent evidence suggests that genetic studies may contribute to a better understanding of individual susceptibility to caries. Matrix metalloproteinases (MMPs) and their tissue inhibitors have been suggested to be involved in the caries process. The purpose of this study was to determine if polymorphisms in MMP2 (rs243865), MMP9 (rs17576), MMP13 (rs2252070), and TIMP2 (rs7501477) were associated with caries. Eligible unrelated children and adolescents were evaluated using a cross-sectional design. Data on oral health habits was obtained through a questionnaire and caries data was collected by clinical examination. Genotyping of the selected polymorphisms was carried out by real-time PCR. Allele and genotype frequencies were compared between individuals with and without caries experience. Of 505 subjects, 212 were caries-free and most subjects (61.2%) had mixed dentition. Allele frequency of MMP2, MMP13 and TIMP2 was different between caries-affected and caries-free individuals, with significant association for MMP13 (p = 0.004). Mutant allele carriers for MMP13 demonstrated a significantly decreased risk for caries (OR = 0.538, 95% CI 0.313-0.926); this result remained significant after adjustment for candidate genes, type of dentition and dietary factors. Allelic and genotype frequencies of the polymorphism in MMP9 were similar in caries-affected and caries-free individuals. Genetic variations in MMP13 may contribute to individual differences in caries susceptibility. Our findings reinforce that susceptibility to caries results from gene-environment interactions. Copyright © 2012 S. Karger AG, Basel