In spite of the many methodological challenges, studies have demonstrated the importance of dietary habits, nutritional status, and chemically determined taste sensitivity with respect to caries risk (Bretz et al., 2006
). We have taken advantage of the growing knowledge of the genetic components of taste preference and dietary habits to investigate the association of taste receptors and pathways with caries, resulting in evidence for association of TAS2R38 and TAS1R2 genotypes and/or haplotypes with caries.
The haplotypes of 3 SNPs representing the corresponding amino acid substitutions (A49P, A262V, V296I) in TAS2R38 have been well-characterized for their influence on the bitter taste sensitivity to specific classes of chemicals, including PROP (propylthiouracil) and PTC (phenylthiocarbamide). The proline, alanine, and valine combination (PAV) represented by the nucleotides (GGC) is associated with bitter sensitivity or “supertasters”, while the alanine, valine, and isoleucine combination (AVI) represented by the nucleotides (CAT) is associated with bitter insensitivity or “non-tasters”. Additional intermediate taster haplotypes, including AAV (CGC) and AAI (CGT), are more rare (Drayna, 2005
). Supertasters have been associated with an increased density of anterior fungiform taste papillae and increased sensitivity to a wide variety of taste and oral sensations, including sweetness, mouth-feel, fats, and oral irritation (reviewed in Tepper, 2008
). Analysis of our data revealed a significant association of the G, G, and C individual alleles representing the P, A, and V substitutions of supertasters with caries protection in the “primary” group. This is further supported by the similar association of the GGC, GGX, and XGC haplotypes. In addition, the CAT haplotype representing the AVI non-taster and CAX haplotype were associated with caries risk. This suggests a role for this gene in caries that may act through influences on dietary habits that then result in differing cariogenic and/or nutritional status.
These results are particularly interesting, considering that phenotypic inversions and other age-related biological responses have been characterized for TAS2R38 haplotypes or chemically determined bitter sensitivity, including correlations to food preferences, liking, and use, including sweet preferences. It has been shown that bitter sensitivity of the TAS2R38 supertaster haplotype declines with age, including a substantial transition during puberty (Bell and Tepper, 2006
). While studies in adults have been inconsistent in correlating bitter sensitivity to sweet sensitivity, a study in preschool children (3.5-4.5 yrs) demonstrated that correlation of PROP determined supertaster children with increased sweet sensitivity, but, strikingly, these supertasters were sweet “likers” and consumed more sweet foods and beverages (Keller and Tepper, 2004
). In another study, the supertaster haplotype of children (5-10 yrs) was similarly correlated to increased sweet sensitivity, liking, and consumption, while the mothers had no correlation to sweet preference (Mennella et al., 2005
). However, the counterintuitive association of the supertaster genotype/haplotype as protective in presumably sweet-liking children suggests that the mechanism is more complex than sugar consumption.
Consumption of fruits and vegetables, especially cruciferous vegetables, has been associated with reduced risk of cancer, with bitterness indicated as the primary reason for avoidance (Drewnowski and Gomez-Carneros, 2000
; Murillo and Mehta, 2001
). In adults, studies investigating the relationship of bitter sensitivity to cruciferous vegetable preferences have been varied (reviewed in Tepper, 2008
). The most consistent relationship appears in studies with preschool children, including two studies showing that preschool non-tasters gave broccoli higher ‘liking’ ratings and consumed more bitter vegetables than preschool supertasters (Keller et al., 2002
; Bell and Tepper, 2006
Other taste and dietary preferences also correlate with bitter sensitivity, including bitter citrus, cheese, and carbonated beverages (reviewed in Tepper, 2008
). Interestingly, comparison of two independent studies of preschool female non-tasters and female college students, respectively, suggested an inversion with age in dietary fat consumption (Yackinous and Guinard, 2002
; Keller and Tepper, 2004
). It is possible that the association of TAS2R38 with caries in the primary dentition may reflect biological processes that change with age, a greater influence of social and cultural influences on adult habits, or a combination of both. While this association is supported by the consistency in the genotype and haplotype associations and could be explained by age-related processes, the potential for undetected association in the mixed and permanent dentitions exists. A larger study group and additional statistical models may be needed to identify associations in these groups, especially if the phenotypic effect is smaller. Additionally, the focus of this analysis on genetic factors does not account for the potential of environmental confounders.
In addition to the influences of the TAS2R38 receptor on taste preferences and dietary habits, a specific sweet receptor has been identified as a heterodimer of the TAS1R2 and TAS1R3 gene products. Analysis of our data revealed a significant association of the C allele of TAS1R2-SNP2 with both caries risk and protection in the “mixed” group. The absence of additional supporting genotype or haplotype association suggests caution in excluding these associations as potential type I errors. However, it is possible that the C allele is interacting with additional SNPs that were not genotyped in our study and are associated separately with caries risk or protection.
In summary, our results have identified two genes important in taste-sensing that are associated with dental caries risk and/or protection. These results highlight the importance of understanding the role of taste preferences in caries and the utility of a genetics approach that overcomes the methodological challenges of laboratory taste preference assessment and reported dietary habits. Ultimately, the characterization of genes involved in taste preference and their genetic association with caries will contribute to greater screening of susceptible individuals and inform intervention strategies. Studies have shown that dietary intervention strategies in infants can have some level of influence on food acceptance (Mennella et al., 2008
). It is possible that different intervention strategies may prove more productive for individual subgroups of taste receptor genotypes and thereby contribute to early and targeted dental caries prevention.