Quinine Bitterness and Grapefruit Liking Associate with Allelic Variants in TAS2R31

Abstract

Multiple psychophysical gene-association studies suggest a single nucleotide polymorphism (SNP) within the bitter receptor gene TAS2R19 on chromosome 12 may be functional. Previously, the Arg299Cys SNP (rs10772420) has been associated with differential bitterness of quinine and differential liking for grapefruit juice. However, quinine does not activate TAS2R19 in vitro; likewise, limonin and naringin, bitter compounds in grapefruit, do not activate TAS2R19 in vitro. Here, we examined quinine bitterness (whole-mouth swish-and-spit stimuli and regionally delivered quinine across 4 loci) and remembered liking for grapefruit juice to test whether they associate with SNPs in another nearby gene, TASR2R31. We observed SNP-phenotype associations between whole-mouth quinine bitterness and self-reported liking for grapefruit juice with SNPs in TAS2R31, and regional quinine bitterness followed a similar trend, but did not reach significance. Present data provide independent replication of prior associations reported for TAS2R19. However, we also observed strong linkage disequilibrium (LD) between TAS2R19 and TAS2R31 SNPs. When present data are considered in light of existing functional expression data, this suggests phenotypic associations reported previously for rs10772420 may potentially be due to LD between this SNP and polymorphism(s) in, or closer to, TAS2R31. If confirmed, this would reduce the number of TAS2Rs with putatively functional polymorphisms to 5.

Keywords: Project GIANT-CS; bitter receptors; bitterness; direct scaling; false positive; linkage disequilibrium (LD); psychophysics; taste.

Figure 1.

Linkage disequilibrium (LD) plot for 3 SNPs (Arg299Cys in TAS2R19; Val240Ile and Ala227 in TAS2R31) on chromosome 12. Numbers indicate rounded R ² values and shading indicates exact R ² values generated via Haploview.

Figure 2.

Quinine bitterness differs by a nucleotide substitution at position 299 in TAS2R19. Consistent with prior reports, individuals who vary in the Arg299Cys SNP (rs10772420) in TAS2R19 differ in the perceived bitterness from whole-mouth 0.41-mM quinine.

Figure 3.

Quinine bitterness differs by TAS2R31 alleles. The perceived bitterness from whole-mouth 0.41-mM quinine differs in individuals who vary in the (a) Val240Ile SNP (rs10772423) and the (b) Ala227Val SNP (rs10845293) in TAS2R31.

Figure 4.

Remembered liking of grapefruit differs by TAS2R19 Arg299Cys alleles. Individuals who vary in the Arg299Cys SNP (rs10772420) in TAS2R19 differ in the remembered liking for unsweetened grapefruit juice.

Figure 5.

Grapefruit liking differs by TAS2R31 alleles. Individuals who vary in the (a) Val240Ile SNP (rs10772423) in TAS2R31 differ in the remembered liking for unsweetened grapefruit juice; a similar pattern was observed for (b) Ala227Val SNP (rs10845293), but the difference was not statistically significant.