Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy.
PLoS One. 2013 Sep 9;8(9):e74151. doi: 10.1371/journal.pone.0074151. eCollection 2013.
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.
味觉对 PROP 的敏感度在个体之间差异很大，与苦味受体基因 TAS2R38 的多态性有关，也与舌前表面味乳头密度的差异有关。最近我们发现，PROP 非味觉者表型与控制唾液营养因子 gustin 的基因 rs2274333（A/G）的 G 变体密切相关。本研究的目的是 1）研究 gustin 基因多态性 rs2274333（A/G）在 PROP 敏感性和味乳头密度和形态中的作用，2）研究 gustin 基因多态性对细胞增殖和代谢活性的影响。通过 PCR 技术对 64 名受试者进行了这两个基因的基因分型，通过标度和阈值方法评估了他们的 PROP 敏感性，并确定了他们的味乳头密度、直径和形态。体外实验研究了个体唾液中 gustin 基因突变和无突变、以及两种同工型分离蛋白处理后细胞增殖和代谢活性的变化。Gustin 和 TAS2R38 基因型与 PROP 阈值相关（p=0.0001 和 p=0.0042），但苦味强度主要由 TAS2R38 基因型决定（p<0.000001）。味乳头密度与两种基因型均相关（p<0.014）（gustin 效应更强；p=0.0006），但味乳头形态仅与 gustin 有关（p<0.0012）。用 gustin 个体 AA 形式的唾液或 gustin 蛋白活性同工型直接处理分离细胞可增加细胞增殖和代谢活性（p<0.0135）。这些新发现表明，gustin 基因的 rs2274333 多态性通过作用于味乳头发育和维持来影响 PROP 敏感性，并可能为 PROP 超级味觉者对广泛的口腔刺激更敏感提供第一个机制解释。
