Association of AXIN2 gene polymorphisms with nonsyndromic oligodontia in Turkish families

Tooth agenesis is the most common developmental abnormality of the human dentition characterized by the congenital absence of one or more permanent teeth. Oligodontia is the term used to describe severe tooth agenesis, where six or more permanent teeth are missing. The WNT gene pathway regulates multiple developmental processes during craniofacial and tooth development, and variations in WNT pathway genes have been reported in individuals with tooth agenesis. In this study, we investigated the association of 37 SNPs in/nearby 12 WNT pathway genes ( WNT3, WNT3A, WNT5A, WNT8A, WNT9B, WNT10A, WNT11, AXIN1, AXIN2, APC, LRP5, LRP6 ) with oligodontia in 22 multiplex families. Genotypes were generated using Taqman chemistry in a real-time polymerase chain reaction assay.  Family-based association tests were performed using FBAT. Pairwise-haplotype analysis was also performed. Bonferroni correction was used to adjust for multiple testing and P-values ≤ 0.001 were considered statistically significant. We found nominal association for AXIN2 rs7591, located in the 3’ UTR, with oligodontia (P=0.04). In silico analysis of SNP function predicted a binding site for miR-205 with potential impact on AXIN2 expression. Although modest, these results continue to support a role for AXIN2 in the etiology of familial tooth agenesis.