Exploring the Association Between Genetic Polymorphisms in Genes Involved in Craniofacial Development and Isolated Tooth Agenesis

Tooth agenesis is a common congenital anomaly in humans and is more common in oral cleft patients than in the general population. Many previous studies suggested that oral cleft and tooth agenesis share a similar genetic background. Therefore, this study explored the association between isolated too...

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Published inFrontiers in physiology Vol. 12; p. 723105
Main Authors Küchler, Erika Calvano, Reis, Caio Luiz Bitencourt, Silva-Sousa, Alice Corrêa, Marañón-Vásquez, Guido Artemio, Matsumoto, Mirian Aiko Nakane, Sebastiani, Aline, Scariot, Rafaela, Paddenberg, Eva, Proff, Peter, Kirschneck, Christian
Format Journal Article
LanguageEnglish
Published Frontiers Media S.A 01.09.2021
Subjects
craniofacial development
dental anomaly
genetic polymorphisms
Physiology
single nucelotide polymorphisms
tooth agenesis
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Abstract Tooth agenesis is a common congenital anomaly in humans and is more common in oral cleft patients than in the general population. Many previous studies suggested that oral cleft and tooth agenesis share a similar genetic background. Therefore, this study explored the association between isolated tooth agenesis and genetic polymorphisms in genes that are crucial for craniofacial and tooth development. Panoramic radiographs, anamnesis, and genomic DNA from 273 patients were included. Patients were classified as tooth agenesis present, when at least one permanent tooth was congenitally missing. Patients with syndromes and oral cleft were excluded. Only unrelated patients were included. The genetic polymorphisms in BMP2 (rs235768 and rs1005464), BMP4 (rs17563), RUNX2 (rs59983488 and rs1200425), and SMAD6 (rs3934908 and rs2119261) were genotyped by real-time polymerase chain reaction. Genotype and allele distributions were compared between the tooth agenesis phenotypes and controls by Chi-square test. Haplotype and diplotype analysis were also performed, in addition to multivariate analysis (alpha of 0.05). A total of 86 tooth agenesis cases and 187 controls were evaluated. For the rs235768 in BMP2 , patients carrying TT genotype have higher chance to present tooth agenesis [ p < 0.001; prevalence ratio (PR) = 8.29; 95% confidence interval (CI) = 4.26–16.10]. The TT genotype in rs3934908 ( SMAD6 ) was associated with higher chance to present third molar agenesis ( p = 0.023; PR = 3.25; 95% CI = 1.17–8.99). BMP2 was also associated in haplotype and diplotype analysis with tooth agenesis. In conclusion, genetic polymorphisms in BMP2 and SMAD6 were associated with isolated tooth agenesis.
AbstractList Tooth agenesis is a common congenital anomaly in humans and is more common in oral cleft patients than in the general population. Many previous studies suggested that oral cleft and tooth agenesis share a similar genetic background. Therefore, this study explored the association between isolated tooth agenesis and genetic polymorphisms in genes that are crucial for craniofacial and tooth development. Panoramic radiographs, anamnesis, and genomic DNA from 273 patients were included. Patients were classified as tooth agenesis present, when at least one permanent tooth was congenitally missing. Patients with syndromes and oral cleft were excluded. Only unrelated patients were included. The genetic polymorphisms in BMP2 (rs235768 and rs1005464), BMP4 (rs17563), RUNX2 (rs59983488 and rs1200425), and SMAD6 (rs3934908 and rs2119261) were genotyped by real-time polymerase chain reaction. Genotype and allele distributions were compared between the tooth agenesis phenotypes and controls by Chi-square test. Haplotype and diplotype analysis were also performed, in addition to multivariate analysis (alpha of 0.05). A total of 86 tooth agenesis cases and 187 controls were evaluated. For the rs235768 in BMP2, patients carrying TT genotype have higher chance to present tooth agenesis [p < 0.001; prevalence ratio (PR) = 8.29; 95% confidence interval (CI) = 4.26–16.10]. The TT genotype in rs3934908 (SMAD6) was associated with higher chance to present third molar agenesis (p = 0.023; PR = 3.25; 95% CI = 1.17–8.99). BMP2 was also associated in haplotype and diplotype analysis with tooth agenesis. In conclusion, genetic polymorphisms in BMP2 and SMAD6 were associated with isolated tooth agenesis.
Tooth agenesis is a common congenital anomaly in humans and is more common in oral cleft patients than in the general population. Many previous studies suggested that oral cleft and tooth agenesis share a similar genetic background. Therefore, this study explored the association between isolated tooth agenesis and genetic polymorphisms in genes that are crucial for craniofacial and tooth development. Panoramic radiographs, anamnesis, and genomic DNA from 273 patients were included. Patients were classified as tooth agenesis present, when at least one permanent tooth was congenitally missing. Patients with syndromes and oral cleft were excluded. Only unrelated patients were included. The genetic polymorphisms in BMP2 (rs235768 and rs1005464), BMP4 (rs17563), RUNX2 (rs59983488 and rs1200425), and SMAD6 (rs3934908 and rs2119261) were genotyped by real-time polymerase chain reaction. Genotype and allele distributions were compared between the tooth agenesis phenotypes and controls by Chi-square test. Haplotype and diplotype analysis were also performed, in addition to multivariate analysis (alpha of 0.05). A total of 86 tooth agenesis cases and 187 controls were evaluated. For the rs235768 in BMP2 , patients carrying TT genotype have higher chance to present tooth agenesis [ p < 0.001; prevalence ratio (PR) = 8.29; 95% confidence interval (CI) = 4.26–16.10]. The TT genotype in rs3934908 ( SMAD6 ) was associated with higher chance to present third molar agenesis ( p = 0.023; PR = 3.25; 95% CI = 1.17–8.99). BMP2 was also associated in haplotype and diplotype analysis with tooth agenesis. In conclusion, genetic polymorphisms in BMP2 and SMAD6 were associated with isolated tooth agenesis.
Author Silva-Sousa, Alice Corrêa
Marañón-Vásquez, Guido Artemio
Scariot, Rafaela
Küchler, Erika Calvano
Matsumoto, Mirian Aiko Nakane
Sebastiani, Aline
Proff, Peter
Reis, Caio Luiz Bitencourt
Kirschneck, Christian
Paddenberg, Eva
AuthorAffiliation 2 Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo , Ribeirão Preto , Brazil
3 Department of Restorative Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo , Ribeirão Preto , Brazil
4 Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Rio de Janeiro , Rio de Janeiro , Brazil
1 Department of Orthodontics, University Medical Centre of Regensburg , Regensburg , Germany
5 Department of Stomatology, Federal University of Paraná , Curitiba , Brazil
AuthorAffiliation_xml – name: 5 Department of Stomatology, Federal University of Paraná , Curitiba , Brazil
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– name: 1 Department of Orthodontics, University Medical Centre of Regensburg , Regensburg , Germany
– name: 3 Department of Restorative Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo , Ribeirão Preto , Brazil
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Copyright Copyright © 2021 Küchler, Reis, Silva-Sousa, Marañón-Vásquez, Matsumoto, Sebastiani, Scariot, Paddenberg, Proff and Kirschneck. 2021 Küchler, Reis, Silva-Sousa, Marañón-Vásquez, Matsumoto, Sebastiani, Scariot, Paddenberg, Proff and Kirschneck
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Edited by: Mohammad Khursheed Alam, Al Jouf University, Saudi Arabia
Reviewed by: Rosa Helena Wanderley Lacerda, Federal University of Paraíba, Brazil; Anand Marya, University of Puthisastra, Cambodia
This article was submitted to Craniofacial Biology and Dental Research, a section of the journal Frontiers in Physiology
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Snippet Tooth agenesis is a common congenital anomaly in humans and is more common in oral cleft patients than in the general population. Many previous studies...
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SubjectTerms craniofacial development
dental anomaly
genetic polymorphisms
Physiology
single nucelotide polymorphisms
tooth agenesis
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Title Exploring the Association Between Genetic Polymorphisms in Genes Involved in Craniofacial Development and Isolated Tooth Agenesis
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