The perception of quinine taste intensity is associated with common genetic variants in a bitter receptor cluster on chromosome 12

Abstract

The perceived taste intensities of quinine HCl, caffeine, sucrose octaacetate (SOA) and propylthiouracil (PROP) solutions were examined in 1457 twins and their siblings. Previous heritability modeling of these bitter stimuli indicated a common genetic factor for quinine, caffeine and SOA (22–28%), as well as separate specific genetic factors for PROP (72%) and quinine (15%). To identify the genes involved, we performed a genome-wide association study with the same sample as the modeling analysis, genotyped for approximately 610 000 single-nucleotide polymorphisms (SNPs). For caffeine and SOA, no SNP association reached a genome-wide statistical criterion. For PROP, the peak association was within TAS2R38 (rs713598, A49P, P = 1.6 × 10−104), which accounted for 45.9% of the trait variance. For quinine, the peak association was centered in a region that contains bitter receptor as well as salivary protein genes and explained 5.8% of the trait variance (TAS2R19, rs10772420, R299C, P = 1.8 × 10−15). We confirmed this association in a replication sample of twins of similar ancestry (P = 0.00001). The specific genetic factor for the perceived intensity of PROP was identified as the gene previously implicated in this trait (TAS2R38). For quinine, one or more bitter receptor or salivary proline-rich protein genes on chromosome 12 have alleles which affect its perception but tight linkage among very similar genes precludes the identification of a single causal genetic variant.

Heritable differences in chemosensory ability among humans

“…It is also possible that the non-tasting form is 'rescued' by other bitter receptors or by other types of genes [29][30][31]. However rescue must be rare, because genome-wide association studies detect no additional phenotype-phenotype associations [14,32].…”

“…For example, identical twins, who have identical genetics, are more similar in their perception of bitter compounds (other than PTC) than are fraternal twins, who are no more similar genetically than siblings [33]. A variant in a cluster of bitter receptors on chromosome 12 is associated with quinine perception [14], and the bitterness of some high-intensity sweeteners is associated with alleles within a cluster of bitter receptors on chromosome 12 [11]. These observations suggest that individual differences in bitter perception may be common, and are related to genotype.…”

The Role of Taste Receptors in Airway Innate Immune Defense

“…Recent work shows that quinine stimulates a rapid T2R-dependent NO response from ciliated cells in the airway [52]. While quinine is a more promiscuous bitter taste receptor agonist than PTC or PROP, there are common genetic variants in bitter taste receptor genes on chromosome 12 that strongly contribute to the perception of quinine taste intensity [53]. Quinine taste sensitivity has also been selected independently in some world populations, especially for low concentrations of quinine [54].…”

Retronasal aroma allows feature extraction from taste of a traditional Japanese confection

“…Gustatory processing of common foods will differ from that observed in experimental evaluations of taste solutions containing a single chemical substance, such as sucrose or citric acid [38][39][40]. For example, consumers perceive the value of sensory evaluation for a particular taste quality after they notice it among other taste qualities.…”