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1.
Genet Epidemiol ; 43(6): 704-716, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31172578

RESUMO

Phenotypic heterogeneity is a hallmark of complex traits, and genetic studies of such traits may focus on them as a single diagnostic entity or by analyzing specific components. For example, in orofacial clefting (OFC), three subtypes-cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP) have been studied separately and in combination. To further dissect the genetic architecture of OFCs and how a given associated locus may be contributing to distinct subtypes of a trait we developed a framework for quantifying and interpreting evidence of subtype-specific or shared genetic effects in complex traits. We applied this technique to create a "cleft map" of the association of 30 genetic loci with three OFC subtypes. In addition to new associations, we found loci with subtype-specific effects (e.g., GRHL3 [CP], WNT5A [CLP]), as well as loci associated with two or all three subtypes. We cross-referenced these results with mouse craniofacial gene expression datasets, which identified additional promising candidate genes. However, we found no strong correlation between OFC subtypes and expression patterns. In aggregate, the cleft map revealed that neither subtype-specific nor shared genetic effects operate in isolation in OFC architecture. Our approach can be easily applied to any complex trait with distinct phenotypic subgroups.

2.
Compend Contin Educ Dent ; 40(6): 342-345; quiz 346, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31166685

RESUMO

Extraction is commonly presented as a treatment alternative for restorable teeth, and patients are biased to choose it for a variety of reasons. However, without subsequent rehabilitation, patients' health, function, and esthetics could be compromised. This article explores problematic outcomes where extraction was offered as a treatment option when teeth were restorable; a case report example demonstrates this issue. The case involved a patient who was diagnosed with moderate to severe periodontitis and had severe attrition and lingual erosion on his maxillary teeth. Despite being given the option of full-mouth rehabilitation, ie, periodontal and restorative treatment, due to financial reasons the patient chose to have all maxillary teeth extracted and receive a maxillary denture. Respecting the patient's autonomy, the dental team performed surgical extraction of the maxillary teeth and an alveoloplasty and delivered an interim denture. The patient did not adapt well to the denture, and several postoperative issues transpired, which required unanticipated surgical procedures. Dissatisfied with the treatment, the patient continued to need dental appointments more than a year after the extractions, and his oral health, function, and esthetics have still not been restored. The dental community must educate patients regarding extraction being an irreversible, last-resource procedure, and mainly indicated only when teeth restoration is not possible. Presenting extraction together with more conservative options for restorable teeth may contribute to patients' misconceptions that it is a treatment alternative as good as any other.

3.
Arch Oral Biol ; 103: 12-18, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31112935

RESUMO

OBJECTIVE: The present cross-sectional, multi-centre, genetic study aimed to determine, whether single nucleotide polymorphisms (SNPs) in tooth agenesis (TA)-associated GLI2 and GLI3 genes contribute to the development of craniofacial skeletal morphology in humans. DESIGN: Orthodontic patients from an ethnically heterogeneous population were selected for the present study (n = 594). The presence or absence of TA was determined by analysis of panoramic radiography and dental records. The subjects were classified according to their skeletal malocclusion and facial growth pattern by means of digital cephalometric analysis. Genomic DNA was extracted from squamous epithelial cells of the buccal mucosa and SNPs in GLI2 (rs3738880, rs2278741) and GLI3 (rs929387, rs846266) were analysed by polymerase chain reaction using TaqMan chemistry and end-point analysis. RESULTS: Class II skeletal malocclusion presented a significantly lower frequency of TA (P < 0.05). Subjects without TA showed significantly higher ANB angles (P < 0.05). Genotype and/or allele distributions of the SNPs in GLI2 (rs3738880, rs2278741) and GLI3 (rs846266) were associated with the presence of TA (P < 0.05). The SNPs rs3738880, rs2278741 and rs929387 were also associated with some type of skeletal malocclusion (P < 0.05), but not with the facial growth pattern (P > 0.05). The G allele for TA-related GLI2 rs3738880 was strongly linked to the presence of Class III skeletal malocclusion (OR = 2.03; 95% CI = 1.37-3.03; P<3125 × 10-6). GLI2 rs2278741 C allele was overrepresented in individuals without TA, suggesting it as a protective factor for this dental phenotype (OR = 0.43; 95% CI = 0.24-0.78; P<625 × 10-5). CONCLUSION: The present study suggests that SNPs in TA-associated GLI2 and GLI3 genes may also play a role in the development of skeletal malocclusions. rs3738880 and rs2278741 in GLI2 seems to contribute to the genetic background for skeletal Class III and TA, respectively. TA could be an additional predictor of craniofacial morphology in some cases. Further research replicating the reported associations should be performed.

4.
Dental Press J Orthod ; 24(2): 92-97, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31116292

RESUMO

INTRODUCTION: Genetics has been suggested as an explanation for the etiology of malocclusions, although some questions, due to the perception that genetic inheritance is tied to a monogenic or Mendelian form of inheritance. OBJECTIVE: This paper describes the inheritance of malocclusions, highlighting the areas of knowledge where research has explored mechanisms that explain deviations in patterns of craniofacial growth. CONCLUSION: Malocclusions have a complex or multifactorial pattern of inheritance, where more than one gene is involved in the development of the phenotype. There is also the possibility that the environment influences malocclusions.

5.
Pediatr Dent ; 41(2): 132-135, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30992111

RESUMO

Purpose: The purpose of this study was to determine if dental ages are more advanced in overweight children and influenced by genetic variation. Methods: Panoramic radiographs from 577 children were obtained. For performing genetic studies, an additional 236 subjects had panoramic radiographs and whole saliva samples collected. Genotyping of IGF, FGF, and FGFR markers was done. Dental age was determined in 177 patients utilizing Demerjian's method and panoramic radiographs. Skeletal maturation was determined in 28 patients using Baccetti's cervical vertebral maturation method on lateral cephalograms. PLINK was used to test for over-representation of alleles. Results: FGF7, FGF10, and FGF13 were significantly associated with obesity (P = 0.02). When dental age was considered, overweight and obese children are more likely to have dental ages more advanced than their chronological ages (P = 0.05). An excess of heterozygotes of FGF18 rs4073716 was found in children with dental age more advanced than their chronological age (P=0.04). Conclusions: Overweight and obese children have dental ages more advanced than their chronological ages, and this occurrence may be influenced by genetic variation in FGF18.


Assuntos
Determinação da Idade pelos Dentes , Variação Genética , Obesidade Pediátrica , Radiografia Panorâmica , Dente/crescimento & desenvolvimento , Determinação da Idade pelo Esqueleto , Índice de Massa Corporal , Vértebras Cervicais/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Fatores de Crescimento de Fibroblastos/genética , Marcadores Genéticos , Humanos , Masculino , Pennsylvania , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor IGF Tipo 2/genética
6.
PLoS One ; 14(4): e0214946, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30973902

RESUMO

Smoking is a leading cause of preventable death. The effect of tobacco is even more contundent in people with mental illness and, in general, cigarette smoking addiction is influenced by genetic factors. The opioid system is involved in the mesolimbic reward system, which is of great importance in addictive behaviors, such as smoking and is influenced by genes such as the OPRM1. The aim of this study was to evaluate if selecting a comparison group that include light smokers versus people that never smoked impacts the results of genetic association studies. In addition, to evaluate the genetic association in different groups of smokers by analyzing independent covariates such as mental illness and clinical dental data. All subjects were participants of the Dental Registry and DNA Repository project. Genotyping was carried out using TaqMan chemistry for two markers in OPRM1 (rs553202 and rs7755635). Logistic regression analyses were performed as implemented in PLINK. The established value for alpha was 5%, and the Hardy-Weinberg equilibrium was evaluated by the chi-square test with one degree of freedom for each marker. 1,897 patients were included, which were allocated to eight distinct groups, according to the frequency and quantity of cigarettes smoked and mental illness status. There was no significant association between the two markers in OPRM1 and smoking. When mental illness and dental clinical data (tooth loss, dental caries, and periodontitis) were used as covariates, there were associations between heavy smoking and OPRM1, when non-smokers were used as comparison. We did not have diet or microbiome data to consider for these dental analyses and suggest that these kinds of data should be always incorporated in the future. Significant results were found only when the covariables mental illness and oral clinical data were added to the analysis.

7.
J Clin Periodontol ; 46(6): 640-641, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31006137

RESUMO

Last January 31st, Journal of Clinical Periodontology just made available the report titled "A Retrospective Analysis of Dental Implant Survival in HIV Patients," which concluded that "implants placed in HIV-positive patients had similar survival rates as HIV-negative patients." These data support our hypothesis that infection by HIV does not lead to worse oral health outcomes, including worse periodontitis. We looked 6,092 individuals and selected all HIV-positive subjects (N = 73) and matched them by age, sex, ethnicity, and smoking habits with 261 HIV-negative control subjects. Based on these 334 total individuals, several dental conditions, including the need for root canal treatment, gingivitis, periodontitis, hairy leukoplakia, and dental caries were compared between the two groups. Overall, there was no difference in dental disease between the HIV-positive and HIV-negative groups. In our data, it was found that the prevalence of periodontitis in HIV-positive patients was 16.4% and in HIV-negative patients 19.2%.

8.
Dental press j. orthod. (Impr.) ; 24(2): 92-97, Mar.-Apr. 2019. graf
Artigo em Inglês | LILACS-Express | ID: biblio-1001858

RESUMO

Abstract Introduction: Genetics has been suggested as an explanation for the etiology of malocclusions, although some questions, due to the perception that genetic inheritance is tied to a monogenic or Mendelian form of inheritance. Objective: This paper describes the inheritance of malocclusions, highlighting the areas of knowledge where research has explored mechanisms that explain deviations in patterns of craniofacial growth. Conclusion: Malocclusions have a complex or multifactorial pattern of inheritance, where more than one gene is involved in the development of the phenotype. There is also the possibility that the environment influences malocclusions.


Resumo Introdução: a genética tem sido proposta como uma explicação para a ocorrência das más oclusões, mas isso é questionável, pois a percepção do significado de herança genética está vinculada à herança mendeliana ou monogênica. Objetivo: o presente artigo visa discorrer sobre a herança das más oclusões e ressaltar as áreas do conhecimento nas quais a pesquisa tem explorado mecanismos que explicam a ocorrência de desvios do padrão de crescimento facial. Conclusão: as más oclusões têm um padrão de herança complexo ou multifatorial, no qual mais de um gene está envolvido no desenvolvimento do fenótipo. Isso quer dizer que existe, também, uma potencial influência do ambiente nas más oclusões.

9.
J Periodontal Res ; 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30900250
10.
Ann Plast Surg ; 82(2): 252, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30628943
11.
Am J Med Genet A ; 179(3): 467-474, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30582786

RESUMO

Genome-wide scans have shown that common risk alleles for orofacial clefts (OFC) tend to be located in noncoding regulatory elements and cumulatively explain only part of the heritability of OFCs. Low-frequency variants may account for some of the "missing" heritability. Therefore, we scanned low-frequency variants located within putative craniofacial enhancers to identify novel OFC risk variants and implicate new regulatory elements in OFC pathogenesis. Analyses were performed in a multiethnic sample of 1,995 cases of cleft lip with or without cleft palate (CL/P), 221 cases with cleft palate (CP) only, and 1,576 unaffected controls. One hundred and nineteen putative craniofacial enhancers identified from ChIP-Seq studies in craniofacial tissues or cell lines contained multiple low-frequency (0.01-1%) variants, which we genotyped in participants using a custom Illumina panel. Two complementary statistical approaches, sequence kernel association test and combined multivariate and collapsing, were used to test association of the aggregated low-frequency variants across each enhancer region with CL/P and CP. We discovered a significant association between CP and a branchial arch enhancer near FOXP1 (mm60; p-value = .0002). Additionally, we observed a suggestive association between CL/P and a forebrain enhancer near FOXE1 (hs1717; p-value = .001). These findings suggest that low-frequency variants in craniofacial enhancer regions contribute to the complex etiology of nonsyndromic OFCs.

12.
Caries Res ; 53(3): 333-338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30580329

RESUMO

Early childhood caries (ECC) is a chronic, infectious disease that affects the primary dentition of young children. It is the result of unequal contributions of risk factors and protective factors that influence the disease. The aim of this study was to assess if the X chromosome region previously linked to caries was associated with ECC. Two hundred and fifty-nine unrelated children with no chronic illnesses from 2 to 5 years of age who had no systemic fluoride consumption were evaluated using a cross-sectional design. Data on oral habits were obtained through a questionnaire, and caries experience data were collected by clinical examination. Twenty-three markers in ten genes were studied. Genotyping of the selected polymorphisms was carried out by real-time polymerase chain reaction. Regression analyses were performed comparing individuals with and without caries experience. Of 259 subjects, 123 were caries free. The markers in Xq25.1-27.2 were associated with ECC when children were using milk bottle for longer times (p = 0.01) and had more snacks over the course of a day (p = 0.05). Conversely, the markers in the X chromosome studied here were protective for ECC (p = 0.008) in children consuming milk before going to sleep. The genes located in the X chromosome possibly contribute to ECC and have an impact on ECC depending on the dietary habits.

13.
Arch Oral Biol ; 97: 85-90, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30366217

RESUMO

OBJECTIVE: This study aimed to evaluate the association of genetic variants inACTN3 and MYO1H with craniofacial skeletal patterns in Brazilians. DESIGN: This cross-sectional study enrolled orthodontic and orthognathic patients selected from 4 regions of Brazil. Lateral cephalograms were used and digital cephalometric tracings and analyzes were performed for craniofacial phenotype determination. Participants were classified according to the skeletal malocclusion in Class I, II or III; and according to the facial type in Mesofacial, Dolichofacial or Brachyfacial. Genomic DNA was extracted from saliva samples containing exfoliated buccal epithelial cells and analyzed for genetic variants inACTN3 (rs678397 and rs1815739) and MYO1H (rs10850110) by real-time PCR. Chi-square or Fisher's exact tests were used for statistical analysis (α = 5%). RESULTS: A total of 646 patients were included in the present study. There was statistically significant association of the genotypes and/or alleles distributions with the skeletal malocclusion (sagittal skeletal pattern) and facial type (vertical pattern) for the variants assessed inACTN3 (P < 0.05). For the genetic variant evaluated in MYO1H, there was statistically significant difference between the genotypes frequencies for skeletal Class I and Class II (P < 0.05). The reported associations were different depending on the region evaluated. CONCLUSION: ACTN3 and MYO1H are associated with sagittal and vertical craniofacial skeletal patterns in Brazilian populations.


Assuntos
Actinina/genética , Variação Genética , Desenvolvimento Maxilofacial/genética , Miosina Tipo I/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Alelos , Brasil , Cefalometria , Estudos Transversais , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Genótipo , Humanos , Masculino , Má Oclusão/genética , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real
15.
Int J Paediatr Dent ; 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30341791

RESUMO

BACKGROUND: Oestrogen (ES) and growth hormone (GH) are hormones that may have a role in caries aetiology and developmental defects of enamel (DDE) since their receptors (ERs and GHR) are expressed during amelogenesis. AIM: To evaluate whether genetic polymorphisms in the genes that codify the ERα (ESR1) and GHR are associated with caries experience and DDE in children. DESIGN: Two hundred and sixteen children of both genders, aged 9-12 years, were examined and classified according to caries and DDE phenotype. Genomic DNA was extracted from buccal cells in saliva. Genetic polymorphisms in ERS1 (rs1884051 and rs12154178) and GHR (rs297305, rs2940913, rs2910875, and rs1509460) were genotyped using TaqMan chemistry. Data were analysed by PLINK, while the chi-square test was used to compare allele and genotype distributions (alpha of 5%). RESULTS: A total of 131 children (60.7%) had caries experience, and 43 (19.9%) presented DDE. Genotype and allele distributions were not associated with caries experience (P > 0.05). Genotype and allele distributions between DDE, affected and unaffected, were associated with the polymorphism rs12154178 in ESR1 (P = 0.01 and P = 0.001, respectively) and with the polymorphism rs1509460 in GHR (P = 0.05 and P = 0.02, respectively). CONCLUSIONS: Genetic polymorphisms in ERS1 (rs12154178) and GHR (rs1509460) are associated with DDE.

16.
Genet Epidemiol ; 42(7): 664-672, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30277614

RESUMO

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans and is notable for its apparent sexual dimorphism where approximately twice as many males are affected as females. The sources of this disparity are largely unknown, but interactions between genetic and sex effects are likely contributors. We examined gene-by-sex (G × S) interactions in a worldwide sample of 2,142 NSCL/P cases and 1,700 controls recruited from 13 countries. First, we performed genome-wide joint tests of the genetic (G) and G × S effects genome-wide using logistic regression assuming an additive genetic model and adjusting for 18 principal components of ancestry. We further interrogated loci with suggestive results from the joint test ( p < 1.00 × 10 -5 ) by examining the G × S effects from the same model. Out of the 133 loci with suggestive results ( p < 1.00 × 10 -5 ) for the joint test, we observed one genome-wide significant G × S effect in the 10q21 locus (rs72804706; p = 6.69 × 10 -9 ; OR = 2.62 CI [1.89, 3.62]) and 16 suggestive G × S effects. At the intergenic 10q21 locus, the risk of NSCL/P is estimated to increase with additional copies of the minor allele for females, but the opposite effect for males. Our observation that the impact of genetic variants on NSCL/P risk differs for males and females may further our understanding of the genetic architecture of NSCL/P and the sex differences underlying clefts and other birth defects.


Assuntos
Alelos , Encéfalo/anormalidades , Fenda Labial/genética , Fissura Palatina/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Caracteres Sexuais , Estudos de Casos e Controles , Epistasia Genética , Feminino , Frequência do Gene/genética , Loci Gênicos , Humanos , Masculino , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Fatores de Risco
18.
Orthod Craniofac Res ; 21(4): 186-201, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30204294

RESUMO

OBJECTIVES: The aim was to review the literature regarding genetic contributions to temporomandibular joint disorder (TMD) after our 2008 publication. SETTING AND SAMPLE POPULATION: Literature review. MATERIAL AND METHODS: PubMed and MEDLINE were used to obtain literature in any language regarding genes and TMD, using the keywords "temporomandibular joint disorder" and "temporomandibular joint dysfunction" for studies published from 2009 to 2017. RESULTS: In our search, 274 studies were found. We excluded 76 studies from animal models, 22 studies that were in vitro and 120 reports that were not cohort or case-control studies. Of the 274 results, 56 articles were selected for this review. Genes that are suggested to contribute to TMD included the ones related to disc and bone alterations as well as pain sensation. CONCLUSION: Currently, no evidence of associated genetic variants, which can determine the development of TMD in individuals, could be translated to novel clinical management and public health strategies for patients suffering from TMD.

19.
Caries Res ; 53(3): 235-241, 2018 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-30205378

RESUMO

The purpose of this cohort study was to identify associations between combined oral and bone disease phenotypes and genes present in cell regulatory pathways. The studied pathways play important roles in cellular growth, proliferation, differentiation, and homeostasis. DNA samples extracted from whole saliva of 3,912 individuals were genotyped and these data analyzed according to dental caries experience, periapical lesions, periodontitis, osteoporosis, or temporomandibular joint discomfort. Samples were obtained from the Dental Registry and DNA Repository project at the University of Pittsburgh. Twenty-seven polymorphisms in eight genes related to mTOR or endoplasmic reticulum stress pathways were selected for genotyping. Allele frequencies and Hardy-Weinberg equilibrium were calculated. Analyses were performed comparing genotypes between affected and unaffected individuals for each phenotype, as well as for the associated phenotypes combined. For all analyses, we used the software PLINK with an alpha of 0.002. Borderline associations with multiple variants of several genes were found, suggesting that both pathways may be involved in the susceptibility to multiple conditions affecting the oral cavity and bones. When combining patients that had concomitant dental caries, periodontitis, and periapical pathology, several markers in RHEB showed statistically significant association. Multiple conditions affecting bone and teeth (i.e., dental caries, periodontitis, periapical lesion formation, and osteoporosis) appear to share similar underlying genetic etiological factors, which allow us to hypothesize that instead of individually, they should be studied in conjunction in human populations.

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