Tooth agenesis-related GLI2 and GLI3 genes may contribute to craniofacial skeletal morphology in humans

Objective: The present cross-sectional, multi-centre, genetic study aimed to determine, whether single nucleotide polymorphisms (SNPs) in tooth agenesis (TA)-associated GLI2 and GLI3 genes contribute to the development of craniofacial skeletal morphology in humans. Design: Orthodontic patients from an ethnically heterogeneous population were selected for the present study (n = 594). The presence or absence of TA was determined by analysis of panoramic radiography and dental records. The subjects were classified according to their skeletal malocclusion and facial growth pattern by means of digital cephalometric analysis. Genomic DNA was extracted from squamous epithelial cells of the buccal mucosa and SNPs in GL12 (rs3738880, rs2278741) and GLI3 (rs929387, rs846266) were analysed by polymerase chain reaction using TaqMan chemistry and end-point analysis. Results: Class II skeletal malocclusion presented a significantly lower frequency of TA (P 0.05). The G allele for TA-related GLI2 rs3738880 was strongly linked to the presence of Class III skeletal malocclusion (OR = 2.03; 95% CI = 1.37-3.03; P < 3125 x 10(-6)). GLI2 rs2278741 C allele was overrepresented in individuals without TA, suggesting it as a protective factor for this dental phenotype (OR = 0.43; 95% CI = 0.24-0.78; P < 625 x 10(-5)). Conclusion: The present study suggests that SNPs in TA-associated GL12 and GLI3 genes may also play a role in the development of skeletal malocclusions. rs3738880 and rs2278741 in GLI2 seems to contribute to the genetic background for skeletal Class III and TA, respectively. TA could be an additional predictor of craniofacial morphology in some cases. Further research replicating the reported associations should be performed