Bone and Cartilage Gene Variants Associated With Anteroposterior Traits in Korean Class III Malocclusion

The purpose of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) of bone-related and cartilage-related genes and the anteroposterior phenotypes of skeletal class III malocclusion. The samples consisted of 310 Korean young adult patients. K-means cluster analysis was performed using the ordinal scales of SNA, SNB, and ANB (normal, moderate, or severe, based on ±1 SD and ±2 SD from the ethnic norm). Three main groups comprising 5 clusters were obtained: (1) class-I group: cluster-4 (normal maxilla and normal mandible), (2) class-II group: cluster-1 (normal maxilla and retrusive mandible), and (3) class-III group: (a) cluster-2 (retrusive maxilla and normal mandible), (b) cluster-5 (normal maxilla and moderately protrusive mandible), and (c) cluster-3 (normal maxilla and severely protrusive mandible). Genotype-phenotype associations were investigated for fibroblast growth factor-10 ( FGF10 )-rs593307, fibrillin-3 precursor gene ( FBN3 )–rs7351083, matrilin1 ( MATN1 )-rs1149042, Wnt family member 11 ( WNT11) -rs1533767, growth hormone receptor ( GHR )-rs2973015 and rs6184, and collagen type-I α1 ( COL1A1 )-rs2249492. Compared with mandibular retrusion (cluster-1), mandibular prognathism was significantly associated with FGF10 -rs593307 and FBN3 -rs7351083 (cluster-3, OR = 2.46~5.12; cluster-3 + cluster-5, OR = 2.46~3.61; all P < 0.05). Compared with a normal mandible (cluster-2), mandibular prognathism was associated with MATN1 -rs1149042 (cluster-3, OR = 4.87; cluster-3 + cluster-5, OR = 3.38; all P < 0.05). Compared with a normal maxilla and retrusive mandible (cluster-1), the combination of a retrusive maxilla and a normal mandible (cluster-2) was associated with FBN3 -rs7351083 (OR = 4.48, P < 0.05). FGF10 -rs593307, FBN3 –rs7351083, and MATN1 -rs1149042 might be associated with skeletal class III malocclusion, specifically through the expression of mandibular prognathism in cluster-3 and cluster-5, and maxillary retrusion in cluster-2.