Self-reported Smoking Status, TAS2R38 Variants, and Propylthiouracil Phenotype: An Exploratory Crowdsourced Cohort Study

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 (similar to 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.