Abstract

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.

Highlights

  • Individual variability in sensitivity to the bitter taste of phenythiocarbamide was first recognized by Fox more than eight decades ago [1]

  • One aim of the present study was to determine the effects of TAS2R38 genotypes and the rs2274333(A/G) polymorphism in the gustin gene on PROP tasting, fungiform papillae density and morphology

  • Results showed that PROP thresholds and bitterness intensity ratings were associated with TAS2R38 and gustin gene genotypes, as reported previously [49]

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Summary

Introduction

Individual variability in sensitivity to the bitter taste of phenythiocarbamide was first recognized by Fox more than eight decades ago [1]. PTC/PROP tasting has gained considerable attention as an oral marker for food preferences and eating habits that impacts nutritional status and health [10] This role is based on data showing that the PROP phenotype associates with variation in perception and preference for fat [11,12,13], energy intake and body weight [14,15], selection of fruits and vegetables [16,17,18], plasma antioxidant status [19] and the risk of colon cancer [20,21,22]. These controversies could be explained by confounding factors (such as cognitive control of eating behavior or the endocannabinoid system) that may play a prominent role in determining these associations [26,27]

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