Response to “Lack of Relation Between Bitter Taste Receptor TAS2R38 and BMI in Adults”

Abstract

TO THE EDITOR: The recent letter by Sausenthaler et al. ((1)) titled “Lack of Relation Between Bitter Taste Receptor TAS2R38 and BMI in Adults” and Tepper's response ((2)) raise two interesting points regarding potential connections between TAS2R38 and adiposity. First, given extent literature on the impact of TAS2R38 on dietary habits, we would not expect a direct effect of TAS2R38 genotype on adiposity, as TAS2R38 is a bitter taste receptor whereas adiposity has a complex multifactor etiology that depends in part on energy intake. Instead, it seems possible, and even likely, that countervailing effects of TAS2R38 variation on energy density washout any simple main effects with regard to adiposity. For example, several reports suggest the PAV allele associates with reduced vegetable intake ((3),(4)). Assuming vegetables displace more energy dense foods from the diet ((5)), we might thus expect AVI carriers to be at less risk for excess weight. Conversely, several studies indicate AVI carriers also consume more alcohol ((6),(7)). Because alcoholic beverage intake may increase adiposity risk directly (via energy density) or indirectly (via dietary disinhibition), we might simultaneously expect AVI carriers to be at greater risk for excess weight. The offsetting effects shown in Figure 1 potentially explain the lack of a direct relationship between TAS2R38 and BMI in spite of mounting evidence that polymorphisms in this gene influence ingestive behavior. Future work must consider these sorts of mediation paths before declaring the absence of a relationship, especially when these mediators may vary substantially across study samples. Countervailing effects of TAS2R38 haplotype on alcohol and vegetable intake potentially explain the null relationship between TAS2R38 and BMI. Second, Tepper's letter reiterates the importance of recent work suggesting the 6-n-propylthiouracil (PROP) phenotype captures additional information that is not provided by genotyping ((8)). Critically, the TAS2R38 genotype only explains part of the variation in PROP phenotype, and that variability in PROP phenotype still explains variation in the intensity of other tastants even after partitioning out effects of genotype. This indicates behavioral measures of PROP bitterness have utility as a predictor of oral sensation that cannot be replaced with a genetic test. Therefore, it is incorrect to assume that PROP phenotype and TAS2R38 genotype are entirely synonymous, as some recent reports have done. Finally, it also should be noted that attempts to connect chemosensory genetics, diet and health should not focus solely on thiourea (PROP and phenylthiocarbamide) phenotypes and genetics, as other taste phenotypes and genotypes also appear to impact food preference and dietary behavior (e.g., ref. (7)). The author declared no conflict of interest.