Genetic Contributions to Dental Caries

Abstract

Source: Shimizu T, Deeley K, Briseño-Ruiz J, et al. Fine-mapping of 5q12.1–13.3 unveils new genetic contributors to caries. Caries Res. 2013; 47(4): 273– 283; doi: 10.1159/000346278Investigators from Nihon University in Japan, the University of Pittsburgh, and multiple other institutions conducted a case-control study to determine if genes within a specific region of chromosome 5 identified in a previous genome-wide association study were associated with dental caries.1 Participants from a larger genetic study conducted in the Philippines were enrolled. Additional individuals from 5 different cultural populations (Turkish, Guatemalan, Argentinean, Brazilian Curitiba, and Brazilian Rio de Janeiro) were enrolled for replication purposes. Each participant provided a saliva sample for DNA and RNA testing and had their dental caries experience assessed by a single examiner. Participants were classified as having high or low caries experience according to their Decayed, Missing and Filled Tooth (DMFT) score. Seventy-five single nucleotide polymorphisms (SNPs) among 50 genes on chromosome 5 were evaluated for each patient. The transmission disequilibrium test was used to determine the association between caries and SNPs. Genes containing SNPs with significant or suggestive associations with caries experience were sequenced to identify the presence of mutations. Also, mRNA expression analysis was performed on individuals with low or high caries experience within one of the replication study populations.Participants included 477 Filipino children and adults (mean age 22.6 years) and 1,467 replication study participants. In the Filipino population, there was a statistically significant association found between low caries experience and 4 genes (PART1, ZSWIM6, CCNB1, and BTF3). In the replication study population, there was a significant association between low caries and a marker in the genes CCNB1 and BTF3. In mRNA analysis, expression of BTF3 was associated with caries experience among children and adolescents and was co-expressed with NFKB1.The authors conclude that the gene BTF3 may function to protect against caries.Dr Slayton has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Dental caries is a complex, multifactorial disease that affects individuals of all ages and socioeconomic backgrounds. While the traditionally held belief is that caries is 100% preventable through management of diet and oral hygiene, investigators have demonstrated that host genetics play a substantial role in both susceptibility and resistance to this disease. Early studies of twins raised apart suggested a heritability of 40% for caries.1 Complex diseases such as dental caries lend themselves to analysis using genome-wide association studies, because with these studies screening of thousands of polymorphism can be done without making any assumptions about what gene might be contributing to the disease. Subsequent candidate gene analysis has identified a number of genes with positive associations with dental caries.2This study was a follow-up to a genome-wide association study focused on identifying loci that contribute to dental caries susceptibility or resistance.3 The sample population used in the previous study was from the Philippines and shared similar cultural background, dietary and oral hygiene habits – all important factors to control for in a genetic study. Because of the co-expression of BTF3 and NFKB1, the authors suggest that this may have an antimicrobial effect on cariogenic microorganisms. Understanding the genetic contributions to caries may allow redefinition of this disease into subcategories based on the etiology rather than the ultimate expression of the phenotype. By characterizing the role these 2 genes play in caries susceptibility, investigators may have the opportunity to develop protective agents and more targeted risk assessment tools for caries.