Candidate Gene Analyses of Skeletal Variation in Malocclusion

Area of Science:

• Genetics
• Orthodontics
• Craniofacial Biology

Background:

• Malocclusion, a common dental condition, has complex etiologies involving both genetic and environmental factors.
• Understanding the genetic basis of craniofacial skeletal variation is crucial for diagnosing and treating malocclusion.

Purpose of the Study:

• To investigate the associations between specific craniofacial candidate genes and skeletal variations in adults with malocclusion.
• To identify genetic markers associated with different types and degrees of malocclusion.

Main Methods:

• Cephalometric radiographs of 269 adults with skeletal malocclusion (Classes I, II, III) were analyzed using principal component analysis (PCA) to define skeletal phenotypes.
• Genotyping was performed for 198 single-nucleotide polymorphisms (SNPs) in 71 craniofacial genes.
• Statistical analyses included multivariate linear regression and multinomial logistic regression to test phenotype-genotype associations.

Main Results:

• PCA identified four principal components explaining 69% of skeletal facial variation, representing vertical discrepancies, maxillomandibular relationships, ramus height, and condylar inclination.
• SNPs near PAX5, SNAI3, MYO1H, TWIST1, and PAX7 were significantly associated with specific craniofacial skeletal variations.
• FGFR2, EDN1, TBX5, and COL1A1 SNPs were associated with increased or decreased risk for skeletal Class II and Class III malocclusion relative to Class I.

Conclusions:

• Specific genes, including PAX5, SNAI3, MYO1H, TWIST1, and PAX7, play a role in craniofacial skeletal variation contributing to malocclusion.
• Genes such as FGFR2, EDN1, TBX5, and COL1A1 are implicated in the determination of malocclusion type (Class II or III).
• These findings contribute to a deeper understanding of the genetic underpinnings of malocclusion, potentially informing future diagnostic and therapeutic strategies.