Genetic polymorphisms associated with developmental defects of enamel: A systematic review.

BACKGROUND: Polymorphisms in genes related to enamel formation and mineralization may increase the risk of developmental defects of enamel (DDE). AIM: To evaluate the existing literature on genetic polymorphisms associated with DDE. DESIGN: This systematic review was registered in the PROSPERO (CRD42018115270). The literature search was performed in PubMed, Scopus, Web of Science, LILACS, BBO, Cochrane Library, and in the gray literature. Observational studies assessing the association between DDE and genetic polymorphism were included. The Newcastle-Ottawa Scale was used to assess the risk of bias. RESULTS: One thousand one hundred and forty-six articles were identified, and 28 met the inclusion criteria. Five studies presented a low risk of bias. Ninety-two genes related to enamel development, craniofacial patterning morphogenesis, immune response, and hormone transcription/reception were included. Molar-incisor hypomineralization (MIH) and/or hypomineralization of primary second molars (HPSM) were associated with 80 polymorphisms of genes responsible for enamel development, immune response, morphogenesis, and xenobiotic detoxication. A significant association was found between the different clinical manifestations of dental fluorosis (DF) with nine polymorphisms of genes responsible for enamel development, craniofacial development, hormonal transcription/reception, and oxidative stress. Hypoplasia was associated with polymorphisms located in intronic regions. CONCLUSION: MIH, HPSM, DF, and hypoplasia reported as having a complex etiology are significantly associated with genetic polymorphisms of several genes.

Association of defects of enamel with polymorphisms in the vitamin D receptor and parathyroid hormone genes.

This cross-sectional study aimed to investigate the association between developmental defects of enamel (DDE) and single nucleotide polymorphisms (SNPs) in the genes encoding the vitamin D receptor (VDR) and parathyroid hormone (PTH). Orthodontic patients receiving treatment at a dental school were selected through convenience sampling. Intra-oral photographs were used to assess DDE, which were classified according to the criteria proposed by Ghanim et al. (2015) by a single calibrated examiner (Kappa>0.80). Enamel hypoplasia, molar-incisor hypomineralization (MIH), hypomimineralized second primary molar (HSPM), and non-MIH/HSPM demarcated opacities were considered for the analysis. Genomic DNA was extracted from buccal cells. The SNPs in VDR (rs7975232) and PHT (rs694, rs6256, and rs307247) were genotyped using real-time polymerase chain reactions (PCR). Statistical analyses were performed using the PLINK software (version 1.03, designed by Shaun Purcell, EUA). Chi-square or Fisher's exact tests were performed at a significance level of 5%. Ninety-one (n=91) patients (49 females and 42 males) (mean age of 14.1±5.8 years) were included. The frequency of DDE was 38.5% (35 patients). Genotype distributions were in Hardy-Weinberg equilibrium. No significant statistical association was found between DDE and the SNPs evaluated. A borderline association (p=0.09) was observed between DDE and the CC haplotype for SNP rs7975232 in VDR. In conclusion, the selected SNPs in VDR and PTH genes were not associated with DDE in the studied samples.

Dentin hypersensitivity and toothache among patients diagnosed with Molar-Incisor Hypomineralization: A systematic review and meta-analysis.

OBJECTIVES: To determine the prevalence of dentin hypersensitivity (DH) and toothache in patients with Molar-Incisor Hypomineralization (MIH); and evaluate whether patients with MIH have greater likelihood of presenting DH/toothache than controls. DATA: Studies evaluating DH/toothache in patients with MIH were included. Studies focusing on other enamel defects were excluded. SOURCES: Eight databases, including grey literature, were searched in January 2024. STUDY SELECTION: The methodological quality of studies was assessed using the Joanna Briggs Institute checklist for Cross-sectional studies. Proportion and association meta-analyses, subgrouped by diagnostic methods, were conducted. The certainty of evidence was assessed using GRADE approach. RESULTS: Fifteen studies were included in the qualitative analysis and fourteen in the meta-analyses. Two studies fulfilled all items of the methodological quality checklist. The overall prevalence of DH/toothache among patients with MIH was 45 %. Prevalence rates of 30 %, 47 %, and 55 % were estimated based on proxy reports, self-reports, and air stimulation, respectively. The overall prevalence of DH/toothache per tooth was 22 %, ranging from 16 % to 29 % according to the diagnostic method. Patients with MIH demonstrated higher likelihood of presenting proxy reports of DH/toothache compared to those without MIH (OR: 1.51, 95 % CI [1.23-1.85], P < 0.01, I2: 0 %). The certainty of evidence was very low, mainly due to the low methodological quality of included studies and high inconsistency. CONCLUSIONS: The global prevalence of DH/toothache was 22 %, per tooth, and 45 % per patient. Estimates vary according to diagnostic methods. Patients with MIH showed higher likelihood of presenting proxy reports of DH/toothache than controls. CLINICAL SIGNIFICANCE: This systematic review contributes valuable information to the dental literature by assessing the prevalence and associated factors of DH/toothache in patients with MIH. The findings can guide future research, inform clinical practices and public policy makers, and ultimately improve the management of oral health of patients with MIH. REGISTRATION: PROSPERO CRD42023432805.

Association between dental age and malocclusions: a systematic review.

BACKGROUND: The evidence in the literature suggests that some skeletal or dental malocclusions are involved with dental development, resulting in advanced or delayed dental age (DA). The purpose of this systematic review was to investigate the association between DA and different types of malocclusions. METHODS: The search was carried out on PubMed, Scopus, Web of Science, Virtual Health Library, and in the gray literature. Observational studies that evaluated the association between DA and sagittal, vertical, or transversal malocclusions were included. The quality assessment was performed using the Newcastle-Ottawa Scale (NOS). The data from primary studies were narratively synthesized. The certainty of evidence was evaluated using the GRADE approach. The study was conducted from August 2023 to October 2023. RESULTS: One Thousand Nine Hundred Ninety-One records were identified in the initial search. Twenty (n = 20) studies were included. Most of the studies (n=15) presented a moderate quality according to NOS. Twelve studies evaluated the association between DA and sagittal discrepancies; eight studies evaluated vertical discrepancies, and only one study analyzed a transversal discrepancy. Demirjian's method for DA assessment was the most used among the studies. The primary studies observed that patients of both sexes presenting a vertical growth pattern and males with skeletal Class III malocclusion tend to have advanced DA. The study that investigated transversal malocclusion found that unilateral posterior cross-bite is associated with delayed DA. The certainty of evidence was very low for all outcomes evaluated. CONCLUSION: DA may be associated with the type of malocclusion. It is suggested that DA can be used as an initial diagnostic tool in orthodontics. Future well-designed studies should be performed in order to investigate the association between DA and different types of malocclusions in more detail. TRIAL REGISTRATION: This study was registered in the PROSPERO database (CRD42023454207).

Association of defects of enamel with polymorphisms in the vitamin D receptor and parathyroid hormone genes

Abstract This cross-sectional study aimed to investigate the association between developmental defects of enamel (DDE) and single nucleotide polymorphisms (SNPs) in the genes encoding the vitamin D receptor (VDR) and parathyroid hormone (PTH). Orthodontic patients receiving treatment at a dental school were selected through convenience sampling. Intra-oral photographs were used to assess DDE, which were classified according to the criteria proposed by Ghanim et al. (2015) by a single calibrated examiner (Kappa>0.80). Enamel hypoplasia, molar-incisor hypomineralization (MIH), hypomimineralized second primary molar (HSPM), and non-MIH/HSPM demarcated opacities were considered for the analysis. Genomic DNA was extracted from buccal cells. The SNPs in VDR (rs7975232) and PHT (rs694, rs6256, and rs307247) were genotyped using real-time polymerase chain reactions (PCR). Statistical analyses were performed using the PLINK software (version 1.03, designed by Shaun Purcell, EUA). Chi-square or Fisher's exact tests were performed at a significance level of 5%. Ninety-one (n=91) patients (49 females and 42 males) (mean age of 14.1±5.8 years) were included. The frequency of DDE was 38.5% (35 patients). Genotype distributions were in Hardy-Weinberg equilibrium. No significant statistical association was found between DDE and the SNPs evaluated. A borderline association (p=0.09) was observed between DDE and the CC haplotype for SNP rs7975232 in VDR. In conclusion, the selected SNPs in VDR and PTH genes were not associated with DDE in the studied samples.

Resumo Este estudo transversal teve como objetivo investigar a associação entre defeitos de desenvolvimento do esmalte (DDE) e polimorfismos de nucleotídeo único (SNPs) nos genes que codificam o receptor da vitamina D (VDR) e o hormônio da paratireoide (PTH). Pacientes ortodônticos em tratamento em uma escola Odontologia foram selecionados por amostragem de conveniência. Os DDEs foram avaliados e classificados por um examinador calibrado (Kappa>0,80) através de fotografias intraorais de acordo com os critérios propostos por Ghanim et al. (2015). Os tipos de DDE considerados para análise foram: hipoplasia de esmalte, hipomineralização molar-incisivo (HMI), hipomineralização de segundos molares decíduos (HSMD) e opacidades demarcadas não-HMI/HSMD. O DNA gnômico foi extraído de células bucais. Os SNPs em VDR (rs7975232) e PTH (rs694, rs6256 e rs307247) foram genotipados por PCR em tempo real. As análises estatísticas foram realizadas utilizando o software PLINK (versão 1.03, concebido por Shaun Purcell, EUA). Foram feitos teste de qui-quadrado e teste exato de Fisher com um nível de significância de 5%. Foram incluídos noventa e um (n=91) pacientes (49 do sexo feminino e 42 do sexo masculino) (idade média de 14,1±5,8 anos). A frequência de DDE foi de 38,5% (35 pacientes). As distribuições genotípicas estavam em equilíbrio de Hardy-Weinberg. Não foi encontrada associação estatisticamente significante entre os DDEs e os SNPs avaliados. Foi observada uma associação limítrofe (p=0,09) entre a DDE e o haplótipo CC para o SNP rs7975232 no VDR. Em conclusão, os SNPs seleccionados nos genes VDR e PTH não foram associados à DDE nas amostras estudadas.

Breastfeeding and Cleft Lip and Palate: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the association between cleft lip and/or cleft palate (CL/P) and breastfeeding (BF). DESIGN: A systematic review and meta-analysis were performed based on studies published in PubMed, Scopus, Web of Science, Cochrane Library, LILACS, BBO, and Embase databases, and in the gray literature. The search occurred in September 2021 and was updated in March 2022. Observational studies evaluating the association between BF and CL/P were included. Risk of bias was analyzed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was conducted. Certainty of evidence was evaluated using the GRADE approach. MAIN OUTCOME MEASURE(S): Frequency of BF in relation to the presence or absence of CL/P, as well as to the type of CL/P. The association between cleft type and BF challenges was also evaluated. RESULTS: From a total of 6863 studies identified, 29 were included in the qualitative review. Risk of bias was moderate and high in most studies (n = 26). There was a significant association between the presence of CL/P and absence of BF (OR = 18.08; 95% CI 7.09-46.09). Individuals with cleft palate with or without cleft lip (CP ± L) had a significantly lower frequency of BF (OR = 5.93; 95% CI 4.30-8.16) and a significantly higher frequency of BF challenges (OR = 13.55; 95% CI 4.91-37.43) compared to individuals with CL. Certainty of the evidence was low or very low in all analyses. CONCLUSION: The presence of clefts, especially those with palate involvement, is associated with higher chances of absence of BF.

Tooth abnormalities associated with non-syndromic cleft lip and palate: systematic review and meta-analysis.

OBJECTIVE: To evaluate the association between orofacial clefts (OFC) and tooth abnormalities (TA). METHODS: We searched PubMed, Scopus, Web of Science, Cochrane Library, LILACS, and BBO, and in the gray literature and selected observational studies that evaluated the association between TA and OFC. The risk of bias was analyzed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed comparing the presence and absence of OFC, cleft type-cleft palate (CP) and cleft lip with or without palate (CL/P)-and cleft laterality-unilateral and bilateral. The certainty of evidence was evaluated using the GRADE approach. RESULTS: A total of 99 studies were included in the qualitative analysis, and 37 were included in the meta-analysis. Only four studies were classified as low risk of bias. Significant associations were observed between the presence of OFC and tooth agenesis (OR = 19.46; 95%CI = 4.99-75.96), supernumerary teeth (OR = 4.04; 95%CI = 1.26-12.99), developmental defects of enamel (OR = 3.15; 95%CI = 1.28-7.80), microdontia (OR = 15.57; 95%CI = 1.06-228.51), and taurodontism (OR = 1.74; 95%CI = 1.74-2.86). Individuals with CP had a lower frequency of supernumerary teeth (OR = 0.22; 95%CI = 0.08-0.64), peg-shaped tooth (OR = 0.31; 95%CI = 0.12-0.80), and morphological TA (OR = 0.13; 95%CI = 0.04-0.45) than individuals with CL/P. No TA was significantly associated with cleft laterality (p > 0.05). The quality of the evidence was very low in all analyses. CONCLUSION: Individuals with OFC had a higher frequency of TA than those without OFC. Individuals with CP had a lower frequency of TA than individuals with CL/P. No TA was associated to cleft laterality. CLINICAL RELEVANCE: Help to identify the treatment needs of individuals affected by OFC, improving the services provided to this population.

What are the Systemic Factors Associated with the Molar-Incisor Hypomineralization Etiology?

ABSTRACT Objective: To evaluate the systemic factors associated with Molar-Incisor Hypomineralization (MIH) etiology. Material and Methods: A total of 731 8-year-old schoolchildren enrolled in the public school system in Curitiba, Brazil, was randomly selected. The MIH diagnosis was performed by calibrated examiners (Kappa >0.80) according to the European Academy of Pediatric Dentistry criteria (2003). The systemic factors were collected through a semi-structured questionnaire and applied to the children's mothers, addressing the medical history from pregnancy to the first three years of children's life. Associations were analyzed by Poisson regression analysis with robust variance (p<0.05). Results: The systemic factors in the prenatal and perinatal periods were not associated with MIH (p>0.05). The children who used medications during the first years of life had a significantly higher prevalence of MIH (PRc = 2.18 CI = 95% 1.06-4.48; p=0.033). Conclusion: The use of medications during the first three years of children's life is associated with a higher prevalence of MIH.