Preventive dental care utilization and dental caries for Medicaid-enrolled adolescents in Oregon.

OBJECTIVES: This study aimed to evaluate the relationship between preventive dental care utilization and untreated dental caries for Medicaid-enrolled adolescents and to determine if the relationship is moderated by chronic conditions (CC). METHODS: This analysis was based on 2015-2016 Medicaid claims files and survey data collected from adolescents ages 12-18 years enrolled in Oregon Medicaid, who received a dental screening between December 2015 and December 2016 (n = 240). To assess the relationship between preventive dental care utilization and untreated dental caries (defined as decayed tooth surfaces), prevalence ratios (PR) and 95% confidence intervals (CI) were generated using log-linear regression models. We also tested for an interaction between preventive dental care utilization and CC. RESULTS: About 60.4% of adolescents utilized preventive dental care, 21.7% had CC, and 29.6% had ≥1 decayed tooth surfaces. There were no significant differences in untreated dental caries between adolescents who did and did not utilize preventive dental care (PR: 0.73, 95% CI: 0.33-1.60; p = 0.43). There was not a significant interaction between preventive dental care utilization and CC (p = 0.65). Preventive dental care utilization was not significantly associated with untreated dental caries for adolescents with CC (PR: 0.51, 95% CI: 0.10-2.65; p = 0.42) nor among adolescents without CC (PR: 0.79, 95% CI: 0.33-1.91; p = 0.61). CONCLUSIONS: Preventive dental care was not shown to be associated with lower untreated dental caries for Medicaid-enrolled adolescents or those with CC. Future work that is adequately powered should continue to elucidate this relationship in Medicaid enrollees.

Functional testing of a human PBX3 variant in zebrafish reveals a potential modifier role in congenital heart defects.

Whole-genome and exome sequencing efforts are increasingly identifying candidate genetic variants associated with human disease. However, predicting and testing the pathogenicity of a genetic variant remains challenging. Genome editing allows for the rigorous functional testing of human genetic variants in animal models. Congenital heart defects (CHDs) are a prominent example of a human disorder with complex genetics. An inherited sequence variant in the human PBX3 gene (PBX3 p.A136V) has previously been shown to be enriched in a CHD patient cohort, indicating that the PBX3 p.A136V variant could be a modifier allele for CHDs. Pbx genes encode three-amino-acid loop extension (TALE)-class homeodomain-containing DNA-binding proteins with diverse roles in development and disease, and are required for heart development in mouse and zebrafish. Here, we used CRISPR-Cas9 genome editing to directly test whether this Pbx gene variant acts as a genetic modifier in zebrafish heart development. We used a single-stranded oligodeoxynucleotide to precisely introduce the human PBX3 p.A136V variant in the homologous zebrafish pbx4 gene (pbx4 p.A131V). We observed that zebrafish that are homozygous for pbx4 p.A131V are viable as adults. However, the pbx4 p.A131V variant enhances the embryonic cardiac morphogenesis phenotype caused by loss of the known cardiac specification factor, Hand2. Our study is the first example of using precision genome editing in zebrafish to demonstrate a function for a human disease-associated single nucleotide variant of unknown significance. Our work underscores the importance of testing the roles of inherited variants, not just de novo variants, as genetic modifiers of CHDs. Our study provides a novel approach toward advancing our understanding of the complex genetics of CHDs.