Suggestive Associations Between Polymorphisms in PAX9, MSX1 Genes and Third Molar Agenesis in Humans

Hypodontia, the congenital agenesis of one or few permanent teeth is among the most common alterations in human dentition. Pax9 and Msx1 genes have critical roles in craniofacial development. Mutations in these genes cause severe tooth agenesis in humans and mice. The aim of the present work was to study the association of the CA repeat in the first intron of MSX1 gene and the C-160T polymorphism in the promoter region of PAX9 gene and hypodontia in humans, with emphasis on third molar agenesis. DNA extracted from buccal epithelial cells was amplified by the Polymerase Chain Reaction. Denaturing Gel Electrophoresis, DNA sequencing and PCR-RLFP were employed on the investigation of the polymorphisms. The 169 bp allele of MSX1-CA repeat was the most prevalent in both groups. Borderline associations were found for MSX1 gene. The 169-bp allele was more frequent in individuals with hypodontia (OR=1.9; 95% CI= 1.0 - 3.6; p=0.05) and 169/175 genotype was less prevalent in individuals with hypodontia (OR=0.4; 95% CI=0.2 - 0.9; p=0.05). The CC genotype of the PAX9 C-160T polymorphism was found at a significant higher frequency in individuals with hypodontia (p=0.0009). A separated analysis of individuals with third molar agenesis also revealed a positive association with the CC genotype (p=0.0007).