TAS2R38 gene variants, which confer sensitivity to specific bitter tastants (e.g., 6-n-propylthiouracil), have been repeatedly associated with lower alcohol use via greater bitterness perception, but research exploring TAS2R38 variation in relation to smoking shows mixed results. In both, the working hypothesis is that 1 or more copies of the functional allele increases bitterness and may provide a barrier to early use. Such a barrier to initiation may, conceivably, manifest as differential rates of current use across diplotypes. Here, an age-diverse convenience sample (n = 886) of Denver Museum of Nature and Science guests was used to explore cross-sectional relationships between TAS2R38 diplotype, self-reported tobacco use (current, former, never smokers), and a rapid measure of 6-n-propylthiouracil phenotype (bitterness of filter paper discs). TAS2R38 diplotypes were determined by Sanger sequencing. After excluding rare diplotypes, data from 814 participants were analyzed. A mix of current (~10%), former (25%), and never smokers (65%) were included. As expected, there was a relationship between TAS2R38 diplotype and 6-n-propylthiouracil bitterness. However, contrary to our hypothesis, there was no evidence of a relationship between diplotype and smoker status among participants with common TAS2R38 diplotypes. Notably, we observed a relationship between of 6-n-propylthiouracil bitterness and smoking status, but the effect was opposite of what was expected: current smokers perceived higher (not lower) bitterness than never smokers. When all the various factors (diplotype, age, sex, and smoking status) were included in ANOVA, all remained predictive of 6-n-propylthiouracil bitterness. Reasons for greater phenotypic bitterness among current smokers are unknown and merit further study.

中文翻译：

---

自我报告的吸烟状况、TAS2R38 变异体和丙基硫氧嘧啶表型：一项探索性众包队列研究。

TAS2R38 基因变异赋予对特定苦味促味剂（例如 6-正丙基硫氧嘧啶）的敏感性，通过增加苦味感知，反复与较低的饮酒量相关，但探索 TAS2R38 变异与吸烟关系的研究显示了不同的结果。在这两种情况下，工作假设是功能性等位基因的 1 个或多个拷贝会增加苦味，并可能为早期使用提供障碍。可以想象，这种启动障碍可能表现为跨双倍型的当前使用率的差异。在这里，丹佛自然科学博物馆客人的年龄多样化便利样本（n = 886）被用来探索 TAS2R38 双倍型、自我报告的烟草使用（现在、以前、从不吸烟者）和快速吸烟之间的横截面关系。 6-正丙基硫氧嘧啶表型的测量（滤纸盘的苦味）。TAS2R38双倍型通过桑格测序确定。排除罕见的双倍型后，对 814 名参与者的数据进行了分析。其中包括当前吸烟者 (~10%)、曾经吸烟者 (25%) 和从不吸烟者 (65%)。正如预期的那样，TAS2R38 二倍型和 6-正丙基硫氧嘧啶苦味之间存在相关性。然而，与我们的假设相反，没有证据表明具有常见 TAS2R38 双倍型的参与者中双倍型与吸烟者状况之间存在关系。值得注意的是，我们观察到 6-正丙基硫氧嘧啶苦味与吸烟状况之间存在关系，但效果与预期相反：当前吸烟者比从不吸烟者感知到更高（而不是更低）的苦味。当所有不同的因素（双倍型、年龄、性别和吸烟状况）都纳入方差分析时，所有因素仍然可以预测 6-正丙基硫氧嘧啶的苦味。当前吸烟者表现型苦味增加的原因尚不清楚，值得进一步研究。