Association Analysis of Class II Division 2 Malocclusion and Two Genes Linked to Hypodontia (MSX1 and PAX9)

Abstract

Purpose of the Study: Determine if there is an association of the CII/D2 malocclusion and genes linked to hypodontia, namely PAX9 and MSX1. Methods and Materials: One hundred probands with CII/D2 and one hundred non-CII/D2 with no hypodontia were enrolled in this study. Clinical exam, photographs, models, radiographs, and saliva were gathered. DNA was isolated from the saliva and sent for genetic analysis. Single Nucleotide Polymorphisms (SNPs) from the PAX9 and MSX1 genes were analyzed using the LightCycler® 480 to verify the presence of each with the CII/D2 malocclusion. A Hardy-Weinberg test was used to screen for genotyping errors, then a chi-square test was used to evaluate the association of the SNP genotypes. A p-value of 0.05 was considered significant. Results: The Hardy-Weinberg test showed no significant differences between observed and expected counts thus we used them for association analysis. Chi-square analysis indicated no significant association between CII/D2 and the MSX1 rs3821949 and the PAX9 1955734 genotypes. Although a p-value of 0.06 for the PAX9 rs8004560 suggested association, it was considered a grey area and insufficient to conclude that there was significant association. Since the SNP PAX9 rs8004560 was insufficient, additional statistical analysis was also performed on the PAX9 rs8004560 genotype of the CII/D2 affected subjects reported to have hypodontia of any tooth including third molars and excluding third molars. A chi-square test yielded a p-value of 0.08 on the analysis of CII/D2 with hypodontia for any permanent tooth except third molars, which suggested association, but insufficient to conclude a significant association. All other analyses indicated a lack of association of the PAX9 rs8004560 SNP. Conclusions: There is no significant association of CII/D2 and the SNPs MSX1 rs3821949 and PAX9 rs1955734. There is a suggestion that there is an association of the SNP PAX9 rs8004560 and CII/D2. There is a suggestion that there is an association of SNP PAX9 rs8004560 and CII/D2 subjects with hypodontia of any tooth except third molars.