Single Nucleotide Polymorphisms in Runt-related Transcription Factor 2 and Bone Morphogenetic Protein 2 Impact on Their Maxillary and Mandibular Gene Expression in Different Craniofacial Patterns - A Comparative Study

Abstract

Introduction: This study aimed to evaluate if single nucleotide polymorphisms (SNPs) in runt-related transcription factor 2 ( RUNX2 ) and bone morphogenetic protein 2 ( BMP2 ) are associated with different craniofacial patterns. Furthermore, we also investigated if RUNX2 and BMP2 expression in the maxilla and mandible are differently expressed according to facial phenotypes and influenced by the SNPs in their encoding genes. Orthognathic patients were included. Materials and Methods: Lateral cephalometric radiographs were used to classify facial phenotypes based on Steiner's ANB and Ricketts’ NBa-PtGn angles. Bone samples from 21 patients collected during orthognathic surgery were used for the gene expression assays. DNA from 129 patients was used for genotyping the SNPs rs59983488 and rs1200425 in RUNX2 and rs235768 and rs1005464 in BMP2 . The established alpha was 5%. Results: A statistically significant difference was observed in the relative BMP2 expression in the mandible between Class I and III participants ( P = 0.042). Homozygous GG (rs59983488) had higher RUNX2 expression ( P = 0.036) in the mandible. In maxilla, GG (rs1200425) had a higher BMP2 expression ( P = 0.038). Discussion: In conclusion, BMP2 is expressed differently in the mandible of Class I and Class III participants. Genetic polymorphisms in RUNX2 and BMP2 are associated with their relative gene expression.

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

“…In this study, we assess the potential impact of SNPs on vertical facial profile establishment. Seven SNPs in well-known genes involved in craniofacial development [ 8 , 10 , 14 ] and associated with skeletal bone physiology [ 17 , 18 , 22 ] were chosen. We reject the null hypothesis; some SNPs in candidate genes may increase the risk of hyperdivergent facial growth.…”

“…In intramembranous growth regions, such as the maxillary sutures and mandibular ramus, RUNX2 is indispensable for the differentiation of pluripotent mesenchymal cells into osteoblasts, while also having a crucial function in mature osteoblasts by sustaining the expression of genes responsible for bone matrix proteins [ 16 ]. Some SNPs in RUNX2 were previously investigated [ 8 , 22 , 25 ] and associated with anteroposterior skeletal malocclusions [ 8 , 22 ]. In this study, the minor allele (A) and recessive genotype (AA) of the rs1200425 were associated with a hyperdivergent profile.…”

“…The rs1200425 is an intronic variant that may induce aberrant mRNA splicing, which is a critical step in the posttranscriptional regulation. The recessive genotype (AA) has already been associated with a decrease in RUNX2 expression in bone tissue [ 22 ]. Interestingly, studies indicate that RUNX2 regulates intramembranous and endochondral growth differently.…”

BMP2 rs1005464 is associated with mandibular condyle size variation

“…What do exist are studies showing that SNPs in genes involved in the aforesaid molecular processes are related to mandibular size and position phenotypes ( i.e. , jaw sagittal and vertical relationships, mandibular retrognathism, mandibular length) 18 – 20 . Considering that condylar dimensions could influence mandibular traits 21 , 22 , it is reasonable to hypothesize that SNPs in endochondral development-related genes might primarily affect the configuration of the mandibular condyle.…”