BMP2 rs1005464 is associated with mandibular condyle size variation

Abstract

This study aimed to evaluate the association between single nucleotide polymorphisms (SNPs) in endochondral development-related genes and mandibular condyle shape, size, volume, and symmetry traits. Cone-beam Computed Tomographies and genomic DNA from 118 individuals were evaluated (age range: 15-66 years). Data from twelve 3D landmarks on mandibular condyles were submitted to morphometric analyses including Procrustes fit, principal component analysis, and estimation of centroid sizes and fluctuating asymmetry scores. Condylar volumes were additionally measured. Seven SNPs across BMP2, BMP4, RUNX2 and SMAD6 were genotyped. Linear models were fit to evaluate the effect of the SNPs on the mandibular condyles' quantitative traits. Only the association between BMP2 rs1005464 and centroid size remained significant after adjusting to account for the false discovery rate due to multiple testing. Individuals carrying at least one A allele for this SNP showed larger condylar size than common homozygotes GG (β = 0.043; 95% CI: 0.014-0.071; P value = 0.028). The model including BMP2 rs1005464, age and sex of the participants explained 17% of the variation in condylar size. Shape, volume, and symmetry were not associated with the evaluated SNPs. These results suggest that BMP2 rs1005464 might be associated with variation in the mandibular condyles size.

Figure 1

Scree plots show the variance explained by symmetric (A) and asymmetric (B) PCs.

Figure 2

Mandibular condyles shape configurations of subjects with the most negative (− β) or positive (+ β) individual scores for symmetric PCs. S—superior, I—inferior, A—anterior, P—posterior, R—right, L—left. Light blue lines represent the average configuration, while dark blue lines represent the variation of interest.

Figure 3

Mandibular condyles shape configurations of subjects with the most negative (− β) or positive (+ β) individual scores for asymmetric PCs. S—superior, I—inferior, A—anterior, P—posterior, R—right, L—left. Light blue lines represent the average configuration, while dark blue lines represent the variation of interest.

Figure 4

3D landmarks on the mandibular condyles. A (black letter)—right side view; B—top view; C—anterior view; S—superior; I—inferior; A (blue letter)—anterior; P—posterior; R—right; L—left; 1 and 3—right and left Sigmoid notch, respectively; 2 and 4—right and left Coronoid process, respectively; 5 and 9—right and left superior Condylion, respectively; 6 and 10—right and left posterior Condylion, respectively; 7 and 11—right and left lateral pole, respectively; 8 and 12—right and left medial pole, respectively.

Figure 5

3D surface models of the mandibular condyles. A (black letter)—right side view; B—top view; C—anterior view; S—superior; I—inferior; A (blue letter)—anterior; P—posterior; R—right; L—left.

Figure 6

Wireframe of the mean configuration of 3D landmarks on the mandibular condyles. A (black letter)—X versus Y axis (side view); B—X versus Z axis (top view); C—Y versus Z axis (anterior view); S—superior; I—inferior; A (blue letter)—anterior; P—posterior; R—right; L—left; 1 and 3—right and left Sigmoid notch, respectively; 2 and 4—right and left Coronoid Process, respectively; 5 and 9—right and left superior Condylion, respectively; 6 and 10—right and left posterior Condylion, respectively; 7 and 11—right and left lateral pole, respectively; 8 and 12—right and left medial pole, respectively.