Taste sensitivity to PROP varies greatly among individuals and is associated with polymorphisms in the bitter receptor gene TAS2R38, and with differences in fungiform papilla density on the anterior tongue surface. Recently we showed that the PROP non-taster phenotype is strongly associated with the G variant of polymorphism rs2274333 (A/G) of the gene that controls the salivary trophic factor, gustin. The aims of this study were 1) to investigate the role of gustin gene polymorphism rs2274333 (A/G), in PROP sensitivity and fungiform papilla density and morphology, and 2) to investigate the effect of this gustin gene polymorphism on cell proliferation and metabolic activity. Sixty-four subjects were genotyped for both genes by PCR techniques, their PROP sensitivity was assessed by scaling and threshold methods, and their fungiform papilla density, diameter and morphology were determined. In vitro experiments examined cell proliferation and metabolic activity, following treatment with saliva of individuals with and without the gustin gene mutation, and with isolated protein, in the two iso-forms. Gustin and TAS2R38 genotypes were associated with PROP threshold (p=0.0001 and p=0.0042), but bitterness intensity was mostly determined by TAS2R38 genotypes (p<0.000001). Fungiform papillae densities were associated with both genotypes (p<0.014) (with a stronger effect for gustin; p=0.0006), but papilla morphology was a function of gustin alone (p<0.0012). Treatment of isolated cells with saliva from individuals with the AA form of gustin or direct application of the active iso-form of gustin protein increased cell proliferation and metabolic activity (p<0.0135). These novel findings suggest that the rs2274333 polymorphism of the gustin gene affects PROP sensitivity by acting on fungiform papilla development and maintenance, and could provide the first mechanistic explanation for why PROP super-tasters are more responsive to a broad range of oral stimuli.

These data showed that responsiveness to PROP is inversely related to BMI and salivary ionic zinc concentrations. The gustin gene dimorphism rs2274333 observed in supertaster and nontaster subjects may influence the protein conformation and, thereby, affect zinc ion binding. Our data showed a direct association between PROP sensitivity and a polymorphism in the gustin gene that is hypothesized to affect its function. This trial was registered at clinicaltrials.gov as UNICADBSITB-1.

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Taste sensitivity to the bitter compound 6-n-propylthiouracil (PROP) is considered a marker for individual differences in taste perception that may influence food preferences and eating behavior, and thereby energy metabolism. This review describes genetic factors that may contribute to PROP sensitivity including: (1) the variants of the TAS2R38 bitter receptor with their different affinities for the stimulus; (2) the gene that controls the gustin protein that acts as a salivary trophic factor for fungiform taste papillae; and (3) other specific salivary proteins that could be involved in facilitating the binding of the PROP molecule with its receptor. In addition, we speculate on the influence of taste sensitivity on energy metabolism, possibly via modulation of the endocannabinoid system, and its possible role in regulating body composition homeostasis.