Associations of Fibroblast Growth Factor Receptor 2 Gene Variants With Anteroposterior and Vertical Phenotypes in Korean Patients With Skeletal Class III Malocclusion.

Efforts to address challenging clinical issues through a deeper understanding of genetics continue to advance in both medicine and dentistry. Given the limited genetic understanding of skeletal Class III malocclusion-a condition that poses significant challenges to both surgeons and orthodontists-this study investigates the association between fibroblast growth factor receptor-2 (FGFR2) gene variants and the anteroposterior and vertical phenotypes of skeletal Class III malocclusion. Genotyping of FGFR2 -SNPs (rs10736303, rs11200014, rs1078806, rs2981578, and rs2162540) was performed in 310 young adults. K -means clustering identified 3 groups with 5 phenotype clusters: Class I (cluster-4, normal maxilla, normal mandible, and normodivergent pattern); Class II (cluster-1, normal maxilla, retrusive mandible, and hyperdivergent pattern); and Class III subtypes: cluster-2 (retrusive maxilla, normal mandible, and hyperdivergent pattern), cluster-5 (normal maxilla, moderately protrusive mandible, and normodivergent pattern), and cluster-3 (normal maxilla, severely protrusive mandible, and normodivergent pattern). Genetic analyses revealed FGFR2 -rs2162540 increased risk of mandibular protrusion (OR=2.13 for cluster-3; OR=4.46 for combined cluster-5/cluster-3, P <0.05), while FGFR2 -rs2981578 and rs10736303 minor alleles heightened mandibular prognathism severity (OR=2.50 and 2.56, respectively; P <0.05). FGFR2 -rs10736303 was also linked to maxillary retrusion and hyperdivergent patterns (OR=3.45 in cluster-2 versus cluster-4, P <0.05). These findings suggest FGFR2 variants significantly contribute to mandibular prognathism, maxillary retrusion, and hyperdivergent growth patterns, providing valuable insights into the genetic etiology of skeletal Class III malocclusion.