Single Nucleotide Polymorphisms in RUNX2 and BMP2 contributes to different vertical facial profile

Caio Luiz Bitencourt Reis; Mirian Aiko Nakane Matsumoto; Maria Bernadete Sasso Stuani; Fábio Lourenço Romano; Rafaela Scariot; Angela Graciela Deliga Schroder; Paulo Nelson-Filho; Christian Kirschneck; Svenja Beisel-Memmert; Erika Calvano Küchler

doi:10.1371/journal.pone.0303551

Single Nucleotide Polymorphisms in RUNX2 and BMP2 contributes to different vertical facial profile

PLoS One. 2024 May 21;19(5):e0303551. doi: 10.1371/journal.pone.0303551. eCollection 2024.

Affiliations

¹ Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
² Department of Stomatology, Federal University of Paraná, Curitiba, Brazil.
³ School of Dentistry, Tuiuti University of Paraná, Curitiba, PR, Brazil.
⁴ Department of Orthodontics, University Hospital Bonn, Medical Faculty, Bonn, Germany.

Abstract

The vertical facial profile is a crucial factor for facial harmony with significant implications for both aesthetic satisfaction and orthodontic treatment planning. However, the role of single nucleotide polymorphisms (SNPs) in the development of vertical facial proportions is still poorly understood. This study aimed to investigate the potential impact of some SNPs in genes associated with craniofacial bone development on the establishment of different vertical facial profiles. Vertical facial profiles were assessed by two senior orthodontists through pre-treatment digital lateral cephalograms. The vertical facial profile type was determined by recommended measurement according to the American Board of Orthodontics. Healthy orthodontic patients were divided into the following groups: "Normodivergent" (control group), "Hyperdivergent" and "Hypodivergent". Patients with a history of orthodontic or facial surgical intervention were excluded. Genomic DNA extracted from saliva samples was used for the genotyping of 7 SNPs in RUNX2, BMP2, BMP4 and SMAD6 genes using real-time polymerase chain reactions (PCR). The genotype distribution between groups was evaluated by uni- and multivariate analysis adjusted by age (alpha = 5%). A total of 272 patients were included, 158 (58.1%) were "Normodivergent", 68 (25.0%) were "Hyperdivergent", and 46 (16.9%) were "Hypodivergent". The SNPs rs1200425 (RUNX2) and rs1005464 (BMP2) were associated with a hyperdivergent vertical profile in uni- and multivariate analysis (p-value < 0.05). Synergistic effect was observed when evaluating both SNPs rs1200425- rs1005464 simultaneously (Prevalence Ratio = 4.0; 95% Confidence Interval = 1.2-13.4; p-value = 0.022). In conclusion, this study supports a link between genetic factors and the establishment of vertical facial profiles. SNPs in RUNX2 and BMP2 genes were identified as potential contributors to hyperdivergent facial profiles.

Copyright: © 2024 Reis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

Adolescent
Adult
Bone Morphogenetic Protein 2* / genetics
Cephalometry
Core Binding Factor Alpha 1 Subunit* / genetics
Face*
Female
Genotype
Humans
Male
Polymorphism, Single Nucleotide*
Young Adult

Substances

RUNX2 protein, human
BMP2 protein, human

Grants and funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001 and Alexander-von-Humboldt-Foundation (Küchler/Kirschneck accepted in July 4th, 2019). The São Paulo Research Foundation (FAPESP) financed individual scholarship (CLBR, process 2021/02704-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.