The Gustin (CA6) Gene Polymorphism, rs2274333 (A/G), as a Mechanistic Link between PROP Tasting and Fungiform Taste Papilla Density and Maintenance

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.

Influences of weight, age, gender, genetics, diseases, and ethnicity on bitterness perception: a narrative review of current methodological aspects

“…The selected studies indicate that receptors of and sensitivity to bitter taste are reduced along life, resulting in a low tolerance threshold among children [48,43,46]. Regarding gender, three articles reported that women are more sensitive to bitter taste also during pregnancy [22,23,43], and one did not find differences between genders regarding the number of gustatory papillae [50]. Different genetic expression, mainly of TAS2R38 and changes in the sensitivity to bitterness sensitivity, have been reported, influencing eating behavior and food preference, including alcohol ingestion [52,53,62].…”

“…Melis et al 2013 [50] Not find any difference between genders, mainly regarding the quantitation of gustatory papillae located on the tongue Bitterness perception and genetics Boxer et al…”

“…Such modification occurs as a protective mechanism, considering that bitterness is mostly recognized as something harmful to the organism [49]. Nevertheless, some authors did not find any difference between genders, mainly regarding the quantitation of gustatory papillae located on the tongue [50].…”

Perceived 6-<i>n</i>-Propylthiouracil (PROP) Bitterness Is Associated with Dietary Sodium Intake in Female Japanese College Students

“…Several molecular mechanisms underlying hyperguesia have been proposed. Polymorphism in the gene for carbonic anhydrase VI, which is highly expressed in the salivary glands and secreted into saliva, has been demonstrated to be associated with individual differences in PROP bitterness and also with fungiform papilla development and maintenance (17,(39)(40)(41)(42), although a recent report has failed to confirm this correlation (43). Salivary peptides belonging to the basic proline-rich protein family have also been implicated in contributing to PROP responsiveness (44,45).…”

Relationships of PROP Taste Phenotype, Taste Receptor Genotype, and Oral Nicotine Replacement Use

“…These findings are consistent with previously reported phenotype-genotype relationships ranging from 55% to 85%. 13,38 Other factors including the number of fungiform papillae 14,39 and TAS2R38 receptor mRNA expression in taste cells 40 may play a role in defining PROP phenotypes.…”