Investigating possible shared single nucleotide polymorphisms in isolated oral cleft and non-cleft facial morphology

IntroductionFacial morphogenesis is regulated by several cellular interactions that are mediated by numerous morphogenetic signals. Based on the existing evidence, we hypothesize that oral cleft-associated single nucleotide polymorphisms (SNPs) are involved in the normal range of human face developm...

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Main Authors: Erika Calvano Küchler, Michelle Nascimento Meger, Bruna Correia Rauta Pires, Svenja Beisel-Memmert, Daniel Hemming, Ricardo D. Coletta, Rafaela Scariot, Mírian Aiko Nakane Matsumoto, Maria Angelica Hueb de Menezes Oliveira, Christian Kirschneck, Bianca Cavalcante-Leão
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Dental Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fdmed.2025.1546295/full
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author Erika Calvano Küchler
Michelle Nascimento Meger
Bruna Correia Rauta Pires
Svenja Beisel-Memmert
Daniel Hemming
Ricardo D. Coletta
Rafaela Scariot
Mírian Aiko Nakane Matsumoto
Maria Angelica Hueb de Menezes Oliveira
Christian Kirschneck
Bianca Cavalcante-Leão
author_facet Erika Calvano Küchler
Michelle Nascimento Meger
Bruna Correia Rauta Pires
Svenja Beisel-Memmert
Daniel Hemming
Ricardo D. Coletta
Rafaela Scariot
Mírian Aiko Nakane Matsumoto
Maria Angelica Hueb de Menezes Oliveira
Christian Kirschneck
Bianca Cavalcante-Leão
author_sort Erika Calvano Küchler
collection DOAJ
description IntroductionFacial morphogenesis is regulated by several cellular interactions that are mediated by numerous morphogenetic signals. Based on the existing evidence, we hypothesize that oral cleft-associated single nucleotide polymorphisms (SNPs) are involved in the normal range of human face development. Therefore, this study aimed to investigate the association between SNPs in oral cleft-related genes and variations in the normal range of facial morphology.MethodA sample of healthy Brazilian teenagers (aged between 11 and 18 years old) were screened and collected. Frontal facial digitized photographs from orthodontic records were used to determine phenotypes, while the DNA extracted from saliva samples was used to investigate the candidate SNPs. Five oral cleft-associated SNPs in BMP2 (rs235768), BMP4 (rs17563), WNT3A (rs708111), WNT11 (rs1533767), and RUNX2 (rs1200425) were selected, and allelic discrimination analysis was performed using real-time PCR.ResultsA total of 58 individuals (27 boys and 31 girls) were included. The facial landmarks used for the facial measurements were the trichion (Tr), glabella (G), nassion (N), subnasale (Sn), labrale superior (Ls), labrale inferior (Li), gnathion (Gn), cheilon (Ch), and zygoma (Zg). rs17563 in BMP4 was associated with lip proportion, in which individuals with the homozygous GG genotype had a higher Ch-Ch:Ls-Li proportion than the heterozygous AG genotype (p = 0.034). rs1533767 in WNT11 was associated with G-Sn:Sn-Gn (p = 0.028), N-Gn:Sn-Gn (p = 0.035), and Sn-Gn:Tr-Gn (p = 0.039).ConclusionOur study supported the hypothesis that oral cleft-associated SNPs are involved in the normal range of human facial morphology.
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spelling doaj-art-dda9e56cefcc48998d5cb261e7e945a62025-08-20T02:16:11ZengFrontiers Media S.A.Frontiers in Dental Medicine2673-49152025-04-01610.3389/fdmed.2025.15462951546295Investigating possible shared single nucleotide polymorphisms in isolated oral cleft and non-cleft facial morphologyErika Calvano Küchler0Michelle Nascimento Meger1Bruna Correia Rauta Pires2Svenja Beisel-Memmert3Daniel Hemming4Ricardo D. Coletta5Rafaela Scariot6Mírian Aiko Nakane Matsumoto7Maria Angelica Hueb de Menezes Oliveira8Christian Kirschneck9Bianca Cavalcante-Leão10Department of Orthodontics, Medical Faculty, University Hospital Bonn, Bonn, GermanySchool of Dentistry, Tuiuti University of Paraná, Curitiba, Paraná, BrazilSchool of Dentistry, Tuiuti University of Paraná, Curitiba, Paraná, BrazilDepartment of Orthodontics, Medical Faculty, University Hospital Bonn, Bonn, GermanySchool of Dentistry, Tuiuti University of Paraná, Curitiba, Paraná, BrazilDepartment of Oral Diagnosis and Graduate Program in Oral Biology, School of Dentistry, University of Campinas, Piracicaba, São Paulo, BrazilDepartment of Stomatology, Federal University of Paraná, Curitiba, Paraná, BrazilDepartment of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, USP—São Paulo University, Ribeirão Preto, São Paulo, BrazilDepartment of Biomaterials, University of Uberaba, Uberaba, Minas Gerais, BrazilDepartment of Orthodontics, Medical Faculty, University Hospital Bonn, Bonn, GermanySchool of Dentistry, Tuiuti University of Paraná, Curitiba, Paraná, BrazilIntroductionFacial morphogenesis is regulated by several cellular interactions that are mediated by numerous morphogenetic signals. Based on the existing evidence, we hypothesize that oral cleft-associated single nucleotide polymorphisms (SNPs) are involved in the normal range of human face development. Therefore, this study aimed to investigate the association between SNPs in oral cleft-related genes and variations in the normal range of facial morphology.MethodA sample of healthy Brazilian teenagers (aged between 11 and 18 years old) were screened and collected. Frontal facial digitized photographs from orthodontic records were used to determine phenotypes, while the DNA extracted from saliva samples was used to investigate the candidate SNPs. Five oral cleft-associated SNPs in BMP2 (rs235768), BMP4 (rs17563), WNT3A (rs708111), WNT11 (rs1533767), and RUNX2 (rs1200425) were selected, and allelic discrimination analysis was performed using real-time PCR.ResultsA total of 58 individuals (27 boys and 31 girls) were included. The facial landmarks used for the facial measurements were the trichion (Tr), glabella (G), nassion (N), subnasale (Sn), labrale superior (Ls), labrale inferior (Li), gnathion (Gn), cheilon (Ch), and zygoma (Zg). rs17563 in BMP4 was associated with lip proportion, in which individuals with the homozygous GG genotype had a higher Ch-Ch:Ls-Li proportion than the heterozygous AG genotype (p = 0.034). rs1533767 in WNT11 was associated with G-Sn:Sn-Gn (p = 0.028), N-Gn:Sn-Gn (p = 0.035), and Sn-Gn:Tr-Gn (p = 0.039).ConclusionOur study supported the hypothesis that oral cleft-associated SNPs are involved in the normal range of human facial morphology.https://www.frontiersin.org/articles/10.3389/fdmed.2025.1546295/fullfacegenespolymorphismcleft lip and/or palatecraniofacial development
spellingShingle Erika Calvano Küchler
Michelle Nascimento Meger
Bruna Correia Rauta Pires
Svenja Beisel-Memmert
Daniel Hemming
Ricardo D. Coletta
Rafaela Scariot
Mírian Aiko Nakane Matsumoto
Maria Angelica Hueb de Menezes Oliveira
Christian Kirschneck
Bianca Cavalcante-Leão
Investigating possible shared single nucleotide polymorphisms in isolated oral cleft and non-cleft facial morphology
Frontiers in Dental Medicine
face
genes
polymorphism
cleft lip and/or palate
craniofacial development
title Investigating possible shared single nucleotide polymorphisms in isolated oral cleft and non-cleft facial morphology
title_full Investigating possible shared single nucleotide polymorphisms in isolated oral cleft and non-cleft facial morphology
title_fullStr Investigating possible shared single nucleotide polymorphisms in isolated oral cleft and non-cleft facial morphology
title_full_unstemmed Investigating possible shared single nucleotide polymorphisms in isolated oral cleft and non-cleft facial morphology
title_short Investigating possible shared single nucleotide polymorphisms in isolated oral cleft and non-cleft facial morphology
title_sort investigating possible shared single nucleotide polymorphisms in isolated oral cleft and non cleft facial morphology
topic face
genes
polymorphism
cleft lip and/or palate
craniofacial development
url https://www.frontiersin.org/articles/10.3389/fdmed.2025.1546295/full
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