Allelic variation in TAS2R bitter receptor genes associates with variation in sensations from and ingestive behaviors toward common bitter beverages in adults

Abstract

The 25 human bitter receptors and their respective genes (TAS2Rs) contain unusually high levels of allelic variation, which may influence response to bitter compounds in the food supply. Phenotypes based on the perceived bitterness of single bitter compounds were first linked to food preference over 50 years ago. The most studied phenotype is propylthiouracil bitterness, which is mediated primarily by the TAS2R38 gene and possibly others. In a laboratory-based study, we tested for associations between TAS2R variants and sensations, liking, or intake of bitter beverages among healthy adults who were primarily of European ancestry. A haploblock across TAS2R3, TAS2R4, and TAS2R5 explained some variability in the bitterness of espresso coffee. For grapefruit juice, variation at a TAS2R19 single nucleotide polymorphism (SNP) was associated with increased bitterness and decreased liking. An association between a TAS2R16 SNP and alcohol intake was identified, and the putative TAS2R38-alcohol relationship was confirmed, although these polymorphisms did not explain sensory or hedonic responses to sampled scotch whisky. In summary, TAS2R polymorphisms appear to influence the sensations, liking, or intake of common and nutritionally significant beverages. Studying perceptual and behavioral differences in vivo using real foods and beverages may potentially identify polymorphisms related to dietary behavior even in the absence of known ligands.

Figure 1

Self-reported alcohol intake frequency in 68 adults. Effects of TAS2R16 SNPs on intake were assessed via ANCOVA, controlling for age (see text). Data represent means ± standard errors. Pairwise comparisons between groups (Fisher least significant difference) are indicated with horizontal lines. This figure appears in color in the online version of Chemical Senses.

Figure 2

Self-reported alcohol intake frequency in 60 adults. Effects of TAS2R38 on intake were assessed via ANCOVA, controlling for age. Genotypes are PAV = PAV/PAV; Het = PAV/AVI; AVI = AVI/AVI; individuals with rare haplotypes were excluded. Data represent means ± standard errors. Pairwise comparisons between groups (Fisher least significant difference) are indicated with horizontal lines. These data are from a new sample of subjects, providing independent confirmation of our earlier report (Duffy et al. 2004). This figure appears in color in the online version of Chemical Senses.

Figure 3

Bitterness intensity ratings of espresso coffee, collected using the gLMS, a psychophysical scale with ratio properties (i.e., a 40 is twice as great as a 20). Effects of the TAS2R3/R4/R5 haploblock were assessed via ANOVA. Genotypes are CCGT = CC,CC,GG,TT; YSRK = C or T, C or G, A or G, G or T; TGAG = TT, GG, AA, GG. Data represent means ± standard errors. Pairwise comparisons between groups (Fisher least significant difference) are indicated with horizontal lines. This figure appears in color in the online version of Chemical Senses.

Figure 4

Bitterness, sweetness, and liking ratings of unsweetened white grapefruit juice. Effects of the TAS2R19 (rs10772420) SNP were assessed via ANOVA. Data represent means ± standard errors. Pairwise comparisons between groups (Fisher least significant difference) are indicated with horizontal lines. This figure appears in color in the online version of Chemical Senses.

Figure 5

LD Plot for TAS2R SNPs on chromosome 7 showing R2 values generated via Haploview. Block 1 indicates a haploblock across TAS2R3, TAS2R4, and TAS2R5 (see text for details), and block 2 indicates the expected PAV/AVI haploblock for TAS2R38. This figure appears in color in the online version of Chemical Senses.