Genetic Polymorphisms in FGFR2 Underlie Skeletal Malocclusion.

Area of Science:

• Genetics
• Orthodontics
• Developmental Biology

Background:

• Fibroblast Growth Factor Receptor 2 (FGFR2) plays a crucial role in craniofacial bone development, regulating osteoprogenitor cells.
• Disruptions in craniofacial bone growth can lead to skeletal malocclusions, such as class II and class III, affecting function and appearance.

Purpose of the Study:

• To investigate the association between genetic variations in FGFR2 and the occurrence of skeletal malocclusions.
• To identify specific FGFR2 single-nucleotide polymorphisms (SNPs) linked to different types of malocclusion.

Main Methods:

• A two-stage case-control study involving 895 subjects with class I, II, and III malocclusions.
• Screening and validation of eight candidate SNPs within the FGFR2 gene.
• Electrophoretic mobility shift assays and chromatin immunoprecipitation to analyze SNP genotype effects on transcription factor binding and gene expression.

Main Results:

• Five FGFR2 SNPs (rs2162540, rs2981578, rs1078806, rs11200014, rs10736303) were significantly associated with skeletal malocclusions (P < 0.05).
• rs2162540 was linked to class II malocclusion, while the other four SNPs were associated with class III malocclusion.
• Specific SNPs (rs2981578, rs10736303) affected RUNX2 and SMAD4 binding, reducing FGFR2 expression and osteogenic differentiation.

Conclusions:

• FGFR2 is identified as a risk gene for skeletal malocclusions.
• FGFR2 polymorphisms modulate its transcriptional expression, thereby influencing osteogenic differentiation and contributing to malocclusion development.