Table 1.
Overview of genetic association studies related to bitter taste preferences.
| Gene | SNP | Applied tastant/method | Number of studies with confirmed association | Findings | Reference | Number of studies with no association | Reference |
|---|---|---|---|---|---|---|---|
| TAS2R38 | rs713598 | PTC, PROP, bitterness of wine/alcohol, food habits questionnaire (liking), detection threshold of methimazole, salicin | 13 (1) | Homozygotes (P49) had the lowest mean thresholds (i.e., greater sensitivity) to both PTC and PROP. The A49P variant demonstrated a strong association with PTC taster status. The variant alleles were inversely associated with bitterness perception of PROP and wine/alcohol. PP conferred to PROP sensitivity. Associated with broccoli score. PP tasters associated with aversion of bitter vegetables and preference of sweet vegetables. Associated with thioamide and salicin detection threshold | (Kim et al., 2003; Ooi et al., 2010; Wooding et al., 2010; Lucock et al., 2011; Colares-Bento et al., 2012; Allen et al., 2013a; Behrens et al., 2013; Allen et al., 2014; Bering et al., 2014; Keller et al., 2014; Mennella et al., 2014a; Carrai et al., 2017; Risso et al., 2017) | 1 | (Mennella et al., 2011a) (PROP, mixed population of children, adolescents, and adults) |
| TAS2R38 | rs1726866 | PTC, PROP, bitterness of wine, food habits questionnaire (liking), detection threshold of methimazole, salicin | 10 (1) | Homozygotes (V296) had the lowest mean thresholds (i.e., greater sensitivity) to both PTC and PROP. Individuals with “A” rather than a “V,” could perceive the bitterness of PROP increased. The variant alleles were inversely associated with bitterness perception of PROP and wine. Associated with broccoli score. Associated with thioamide and salicin detection threshold | (Kim et al., 2003; Wooding et al., 2010; Lucock et al., 2011; Mennella et al., 2011a; Allen et al., 2013a; Behrens et al., 2013; Bering et al., 2014; Robino et al., 2016; Carrai et al., 2017; Risso et al., 2017) | 2 | (Duffy et al., 2004a; Timpson et al., 2007) (AceK bitterness, bitterness of alcohol) |
| TAS2R38 | rs10246939 | PROP, bitterness of wine/alcohol, food habits questionnaire (liking), detection threshold of methimazole, salicin | 8 (1) | Individuals with a “V” in the last position were more likely to detect bitterness at the lowest concentration compared with subjects with the same diplotype but with an “I” in the last position. The variant alleles were inversely associated with bitterness perception of PROP and wine. Associated with broccoli score. Associated with thioamide and salicin detection threshold | (Lucock et al., 2011; Mennella et al., 2011a; Behrens et al., 2013; Allen et al., 2014; Bering et al., 2014; Ledda et al., 2014; Carrai et al., 2017; Risso et al., 2017) | 0 | – |
| TAS2R38 | A49P (rs713598), A262V (rs1726866) | PROP | 2 | Associated with PROP phenotype | (Timpson et al., 2007; Bering et al., 2014) | 0 | – |
| TAS2R38 | A49P (rs713598), A262V (rs1726866) | Cruciferous/Brassica vegetable intake (24-hour dietary recall, food record) | 1 (1) | Haplotype associated with cruciferous vegetable intake | (Sacerdote et al., 2007) | 1 (Popkin, 2006) | (Inoue et al., 2013) |
| TAS2R38 | A49P (rs713598), A262V (rs1726866), V296I (rs10246939) | PTC, PROP, food habits questionnaire (liking), bitterness of nonglucosinolate-generating vegetables, bitterness of alcohol, liking and bitterness perception of salad rocket, detection threshold of methimazole, salicin | 23 (4) | PAV homozygotes possessed a greater sensitivity to PTC compared with AVI. Taster PAV haplotypes inversely correlated with broccoli score and positively associated with PROP perceived bitterness. PAV/PAV subjects rated the glucosinolate-generating vegetables more bitter, than AVI/AVI subjects. Bitterness of ethanol differed significantly among haplotypes. Associated with bitterness perception and scores of salad rocket. Associated with thioamide and salicin detection threshold | (Kim et al., 2003; Duffy et al., 2004a; Mennella et al., 2005; Sandell and Breslin, 2006; Hayes et al., 2008; Duffy et al., 2010; Wooding et al., 2010; Calò C et al., 2011; Lucock et al., 2011; Cabras et al., 2012; Negri et al., 2012; Campbell et al., 2012; Melis et al., 2013; Allen et al., 2014; Bering et al., 2014; Garneau et al., 2014; Robino et al., 2014; Melis et al., 2015; Nolden et al., 2016; Bella et al., 2017; Deshaware and Singhal, 2017; Risso et al., 2017in children also, Behrens et al., 2013) | 2 | (Feeney et al., 2017) |
| TAS2R38 | A49P (rs713598), A262V (rs1726866), V296I (rs10246939) | Bitterness of berry juice samples and extracts (bilberry, crowberry) | 1 (1) | AVI/AVI subjects rated bitterness, higher than the PAV/PAV subjects | (Laaksonen et al., 2013) | 0 | – |
| TAS2R38 | A49P (rs713598), A262V (rs1726866), V296I (rs10246939) | Brassica vegetable intake (FFQ) | 1 (1) | Associated with consumption of bitter-tasting vegetables (only in children) | (Feeney et al., 2011) | 2 (1) | (Gorovic N et al., 2011; Negri et al., 2012) |
| TAS2R19 | rs10772420 | Quinine, detection and recognition thresholds, perceived bitter taste intensities of absinthin, amarogentin, cascarillin, grosheimin, quassin, and quinine, PROP bitterness of unsweetened grapefruit juice | 5 | Associated with quinine intensity ratings. A allele was associated with more intense quinine perception. Associated with grosheimin detection threshold and intensities (weak, moderate, strong, very strong). Individuals who were homozygous for the Cys299 allele rated grapefruit juice twice as bitter and liked it less as Arg299 homozygotes or heterozygotes. | (Reed et al., 2010; Hayes et al., 2011; Knaapila et al., 2012; Hayes et al., 2015; Roudnitzky et al., 2015) | 1 | (Bering et al., 2014) (PROP) |
| TAS2R19 | rs1868769 | Quinine, detection and recognition thresholds, perceived bitter taste intensities of absinthin, amarogentin, cascarillin, grosheimin, quassin, and quinine, PROP | 2 | Associated with quinine intensity ratings. Associated with grosheimin detection threshold, recognition threshold, and weak intensity | (Knaapila et al., 2012; Roudnitzky et al., 2015) | 1 | (Bering et al., 2014) (PROP) |
| TAS2R31 (formerly TAS2R44) | rs10845293 | Detection and recognition thresholds, perceived bitter taste intensities of absinthin, amarogentin, cascarillin, grosheimin, quassin, and quinine, saccharin recognition threshold, bitterness of acesulfame potassium | 6(1) | Associated with grosheimin detection threshold and intensities (weak, moderate, strong, very strong). Associated with saccharin response. Individuals with at least one TAS2R44-W35 allele were more sensitive to saccharin compared to the group homozygous for the hTAS2R44-R35 allele. Val227 homozygotes reported less bitterness from AceK than the Ala227 homozygotes (heterozygotes intermediate). Association with quinine bitterness | (Pronin et al., 2007; Roudnitzky et al., 2011; Allen et al., 2013a; Allen et al., 2013b; Hayes et al., 2015; Roudnitzky et al., 2015) | 1 | (Timpson et al., 2007) (PROP) |
| TAS2R31 (formerly TAS2R44) | rs10772423 | Detection and recognition thresholds, perceived bitter taste intensities of absinthin, amarogentin, cascarillin, grosheimin, quassin, and quinine, bitterness of acesulfame potassium, grapefruit liking | 3 | Associated with amarogentin intensity (weak), grosheimin detection threshold, recognition threshold, and intensities (weak, moderate, strong, very strong intensity). Val240 homozygotes reported less bitterness from AceK than the Ile240 homozygotes (Val/Ile heterozygotes intermediate). Association with quinine bitterness and grapefruit liking | (Allen et al., 2013b; Hayes et al., 2015; Roudnitzky et al., 2015) | 1 | (Nolden et al., 2016) (Bitterness of capsaicin, piperine, ethanol) |
| TAS2R4 | rs2234001 | Bitterness of stevioside, bitterness of unsweetened grapefruit juice, instant espresso | 2 | Bitterness of stevioside positively associated with G allele. Haplotype, allelic variation (TAS2R3, -R4, and -R5) explained variability in coffee bitterness [individuals with one or two copies of the more responsive haplotype (TGAG) experienced twice as much bitterness compared with individuals homozygous for the less responsive haplotype (CCGT), but these haplotypes did not predict coffee liking]. | (Hayes et al., 2011; Risso et al., 2017) | 4 | (Duffy et al., 2004a; Pronin et al., 2007; Timpson et al., 2007; Lucock et al., 2011) (PROP, AceK bitterness) |
| TAS2R5 | rs2227264 | Bitterness of unsweetened grapefruit juice, instant espresso, PROP | 2 | Haplotype, allelic variation (TAS2R3, -R4, and -R5) explained variability in coffee bitterness [individuals with one or two copies of the more responsive haplotype (TGAG) experienced twice as much bitterness compared with individuals homozygous for the less responsive haplotype (CCGT), the haploblock did not predict coffee liking]. Associated with PROP phenotype | (Hayes et al., 2011; Carrai et al., 2017) | 0 | – |
| TAS2R5 | rs2234012 | Bitterness of unsweetened grapefruit juice, instant espresso, intake, PROP | 2 | Haplotype, allelic variation (TAS2R3, -R4, and -R5) explained variability in coffee bitterness [individuals with one or two copies of the more responsive haplotype (TGAG) experienced twice as much bitterness compared with individuals homozygous for the less responsive haplotype (CCGT), the haploblock did not predict coffee liking]. Associated with PROP phenotype | (Hayes et al., 2011; Nolden et al., 2016) | 0 | – |
| TAS2R9 | rs3741845 | Bitterness of acesulfame potassium, bitterness of capsaicin, piperine, ethanol | 2 | Ala187 homozygotes reported less bitterness than heterozygotes and the Val187 homozygotes. | (Pronin et al., 2007; Timpson et al., 2007) | 2 | (Sandell and Breslin, 2006; Timpson et al., 2007) (PROP) |
| CA6 | rs2274333 | PROP | 4 (1) | The genotype AA and allele A were more frequent in supertasters, whereas genotype GG and allele G were more frequent in non-tasters. GG vs. AA or AG had thresholds that were more than 10-fold higher. Supertasters had a very high frequency of genotype AA and allele A, whereas non-tasters had a higher frequency of genotype GG and allele G. PROP super-tasters had a very high frequency of allele A, whereas non-tasters had a higher frequency of allele G. | (Padiglia et al., 2010; Calò C et al., 2011; Cabras et al., 2012; Melis et al., 2013) | 3 | (Bering et al., 2014; Feeney and Hayes, 2014; Risso et al., 2017) |
Number of low quality studies is presented in parentheses.
PTC, phenylthiocarbamide; PROP, 6-n-propylthiouracil; FFQ, food frequency questionnaire; AceK, acesulfame potassium.