Evidence of Association between IRF6 and Tooth Agenesis in Turkey

Objective: Inheritance is the major factor of tooth agenesis in humans. MSX1 and PAX9 are genes that cause severe forms of isolated human tooth agenesis but are responsible for a small percentage of the cases. Genes involved in syndromic forms of tooth agenesis are interesting candidates for the isolated forms. Van der Woude syndrome is the most common monogenic form of clefting and presents itself with lip pits and tooth agenesis in 20% to 40% of the cases, particularly incisors and premolars. The aim of this study was to investigate the possible association between IRF6, which mutations cause Van der Woude syndrome, and tooth agenesis in Turkish families.

Method: Fifty-three nuclear families (father-mother-affected child-siblings) whose proband presented tooth agenesis except for third molars were studied. Saliva or whole blood DNA amplified by PCR using TaqMan chemistry was tested by FBAT (Family Based Association Test) to measure the transmission distortion of alleles and haplotypes.

Results: An association between the IRF6 rs642961 marker and tooth agenesis was found (p = 0.04). In addition, the IRF6 haplotypes rs861019-rs2073487-rs642961 (p = 0.03) and rs2073487-rs642961-rs658860 (p = 0.006) were overtransmitted to tooth agenesis affected individuals. An association could still be seen when only cases with at least one missing incisor (p=0.01) and cases with at least one missing premolar (p=0.004) were included in the analysis.

Conclusion: These results confirm the original reported association between IRF6 and tooth agenesis and indeed suggest that IRF6 plays a role in this congenital anomaly.