OMICS A Journal of Integrative Biology

Volume 13, Number 1, 2009

© Mary Ann Liebert, Inc.
DOI: 10.1089/omi.2008.0031

Review

Genetic Variation in Taste and Its Influence

on Food Selection

Bibiana Garcia-Bailo, Clare Toguri, Karen M. Eny, and Ahmed El-Sohemy

Abstract

Taste perception plays a key role in determining individual food preferences and dietary habits. Individual dif-
ferences in bitter, sweet, umami, sour, or salty taste perception may influence dietary habits, affecting nutri-
tional status and nutrition-related chronic disease risk. In addition to these traditional taste modalities there is
growing evidence that “fat taste” may represent a sixth modality. Several taste receptors have been identified
within taste cell membranes on the surface of the tongue, and they include the T2R family of bitter taste re-
ceptors, the T1R receptors associated with sweet and umami taste perception, the ion channels PKD1L3 and
PKD2L1 linked to sour taste, and the integral membrane protein CD36, which is a putative “fat taste” recep-
tor. Additionally, epithelial sodium channels and a vanilloid receptor, TRPV1, may account for salty taste per-
ception. Common polymorphisms in genes involved in taste perception may account for some of the in-
terindividual differences in food preferences and dietary habits within and between populations. This variability
could affect food choices and dietary habits, which may influence nutritional and health status and the risk of
chronic disease. This review will summarize the present state of knowledge of the genetic variation in taste,
and how such variation might influence food intake behaviors.

Introduction taste modality (Laugerette et al., 2005). Perception of each of

these taste modalities appears to be mediated by a different

I NDIVIDUALS MAKE FOOD CHOICES based on a number of phys-

iological, nutritional, environmental, and sociocultural
factors. However, the sensory qualities of food are critical to
dietary preferences, and taste in particular may be the most
important determinant of food choices (Drewnowski and
Rock, 1995; Glanz et al., 1998; Leterme et al., 2008). Taste per-
ception occurs when chemical molecules from food reach mi-
crovilli located at the apical tip of taste receptor cells (TRCs)
(Chandrashekar et al., 2006; Ishimaru et al., 2006; Linde-
mann, 2001). TRCs congregate in groups of 50 to 100 to form
onion-shaped taste buds (Bachmanov and Beauchamp, 2007;
Ishimaru et al., 2006; Lindemann, 2001). Taste buds, in turn,
cluster into circumvallate, foliate, or fungiform papillae, and
mammalian papillae are located in epithelial surfaces of the
tongue, palate, pharynx, larynx, and upper esophagus
(Chandrashekar et al., 2006; Kataoka et al., 2008; Lindemann,
2001).
The vast array of flavors, defined as overall sensory per-
ception, found in foods is triggered by only a few, distinct
taste modalities: bitter, sweet, salty, sour, and umami (sa-
vory) (Bachmanov and Beauchamp, 2007; Roper, 2007).
There is growing evidence that “fat” may also be a distinct
mechanism, although the molecular basis for some of them
remains relatively obscure. Ion channels in TRCs account for
salty taste perception (Drayna, 2005), while different G-pro-
tein coupled receptors bind bitter (Adler et al., 2000; Chan-
drashekar et al., 2000; Matsunami et al., 2000), sweet (Li et
al., 2002), and umami tastants (Nelson et al., 2002). Sour tas-
tants are detected by members of the transient receptor po-
tential ion channel family (Huang et al., 2006; Ishimaru et al.,
2006; LopezJimenez et al., 2006). The genes encoding several
of these receptors have been identified, and they include the
TAS2R gene family for bitter (Adler et al., 2000; Chan-
drashekar et al., 2000; Matsunami et al., 2000), the TAS1R
family for sweet and umami (Bachmanov et al., 2002; Li et
al., 2002), and PKD2L1 and PKD1L3 for sour taste (Huang et
al., 2006; Ishimaru et al., 2006; LopezJimenez et al., 2006). In
addition, the fatty acid transporter CD36 has been recently
identified as a putative taste receptor for fat (Laugerette et
al., 2005).
Genetic variation in taste receptors may account for dif-
ferences in food choices and dietary habits. Polymorphisms
of the genes that code for taste receptors may explain some
of the observed variability in taste perception. This variabil-

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, M5S 3E2, Canada.

69
70
ity could affect food choices and dietary habits, and might
influence nutritional and health status, as well as the risk of
chronic disease (Fig. 1). This review will provide a summary
of the current knowledge of taste perception mechanisms
and genetic variation in taste, and how such variation might
influence food intake behaviors.
Bitter Taste
Bitter has been the most extensively studied taste modal-
ity. Bitter tasting compounds are ubiquitous in nature and
structurally diverse at the molecular level (Chandrashekar
et al., 2006; Kim et al., 2004). Many bitter tasting substances
are noxious, and bitter taste perception probably evolved to
prevent the consumption of plant toxins (Chandrashekar et
al., 2006; Drewnowski and Rock, 1995; Kim and Drayna,
2004). Bitter stimuli elicit rejection responses in young chil-
dren and nonhuman primates (Roper, 2007). However, di-
etary sources of bitter tastants are common, and they include
nutritionally significant plants such as spinach, endives, and
many cruciferous vegetables, such as broccoli, bok choy,
kale, cauliflower, cabbage, watercress, and arugula. Other
bitter-tasting foods include sharp cheeses, soy products,
grapefruit, beer, green tea and coffee (Anliker et al., 1991;
Drewnowski et al., 2001; Duffy and Bartoshuk, 2000; Kamin-
ski et al., 2000; Keller et al., 2002; Prescott et al., 2004; Turn-
bull and Matisoo-Smith, 2002). These foods contain bitter-
tasting phytochemicals such as isothiocyanates resulting
from glucosinolate breakdown in cruciferous vegetables, as
well as polyphenols, methylxanthines, isoflavones, and sul-
famides. All of these phytochemicals might protect against
a number of illnesses (Basson et al., 2005; Drewnowski and
Rock, 1995; El-Sohemy et al., 2007; Timpson et al., 2005). In-
dividuals who perceive these compounds as more intensely
bitter may avoid consuming them, and this could affect their
nutritional and health status.
Bitter taste perception is a variable trait, and its genetic ba-
sis was identified over 75 years ago through a series of stud-
ies on individual responses to phenylthiocarbamide (PTC)
(Blakeslee, 1932; Fox, 1931). PTC and the related compound
6-n-propylthiouracil (PROP) are members of the thioureas
and contain a thiocyanate moiety (N-C  S) (Bartoshuk et
al., 1994; Tepper, 1998). While PTC and PROP do not occur
naturally in foods, they elicit a bitter taste stimulus in some
individuals. The variability in response to their taste corre-
lates with taste sensitivity to other bitter substances present
in foods (Barnicot et al., 1951; Blakeslee and Salmon, 1935;
Drewnowski and Rock, 1995; Hall et al., 1975). Thus, PTC
FIG. 1. Gene association studies have linked genetic variation in taste receptors to risk of disease. This can occur through
differences in taste perception, which may lead to differences in food preferences and food intake. This variation in food
intake may, in turn, affect metabolism and health outcomes.
GARCIA-BAILO ET AL.
and PROP are often used in taste perception studies to as-
sess the link between genetics and bitter taste perception. A
recent review covers PTC and PROP tasting study method-
ologies and evolutionary implications of these phenotypes,
and offers an in-depth summary of their association with
food acceptance (Tepper, 2008).
Overall, about 75% of humans find PTC and PROP bitter
in taste, and they are classified as “tasters.” The remainder
of the population finds PTC and PROP tasteless and are con-
sidered “nontasters” (Kim and Drayna, 2004). The propor-
tion of nontasters varies between populations across the
globe. In West Africa, 3% of the population is blind to the
bitter taste of PTC and PROP, but in China the proportion
ranges between 6% and 23%, and in India it has been re-
ported to be as high as 40%. Caucasian North American pop-
ulations exhibit a nontaster frequency of about 30% (Guo and
Reed, 2001; Tepper, 1998). While the distribution of sensi-
tivity to PTC/PROP bitterness was traditionally described
as bimodal, increasing evidence suggests that the trait dis-
plays a broad, continuous distribution (Bartoshuk et al., 1994;
Kim and Drayna, 2004). Within the portion of the popula-
tion that can taste PTC/PROP, there exists variability in the
perceived degree of bitterness such that tasters can be sub-
divided into medium tasters and supertasters (Bartoshuk et
al., 1994; El-Sohemy et al., 2007). Additionally, increased sen-
sitivity to bitter taste has been hypothesized to correlate with
greater general taste acuity. A number of studies have found
associations between increased bitterness sensitivity and
heightened responses to sweet (Bartoshuk et al., 1994; De-
Simone and Lyall, 2006; Duffy et al., 2004; Mennella et al.,
2005) and salty stimuli (Bartoshuk et al., 1998). Oral irritants
such as capsaicin and ethanol also elicit heightened re-
sponses among PTC/PROP tasters (Prescott and Swain-
Campbell, 2000). Furthermore, tasters show increased sensi-
tivity to olfactory cues (Pickering et al., 2006) and to viscous
substances such as fats and food thickeners (Bartoshuk,
2000).
Research conducted in the last decade has shown that bit-
ter taste perception is mediated by the T2Rs, a family of G
protein-coupled taste receptors with seven trans-membrane
domains and a short extracellular N-terminus (Bachmanov
and Beauchamp, 2007; Roper, 2007). T2Rs are located at the
surface of taste cells within circumvallate and foliate papil-
lae, and to a lesser extent within fungiform papillae. They
are also present in the palate and epiglottis (Adler et al., 2000;
Bachmanov and Beauchamp, 2007; Chandrashekar et al.,
2000; Matsunami et al., 2000). In humans, T2Rs are encoded
by about 25 functional TAS2R genes located on chromo-
GENETIC VARIATION IN TASTE
somes 5, 7, and 12 (Drayna, 2005; Tepper, 2008). Bachmanov
and Beauchamp (2007) provide a thorough review of the dis-
covery and genomic organization of these and other taste re-
ceptor genes.
Over the past several years, efforts have been made to link
T2R bitter taste receptors to particular tastants (Bufe et al.,
2002; Kuhn et al., 2004). In particular, TAS2R38 has been
identified as the gene for PTC sensitivity (Kim et al., 2003).
TAS2R38, located on chromosome 7q, consists of a single
1002-bp long exon that encodes a 333-amino acid, 7 trans-
membrane-spanning domain, guanine nucleotide-binding
protein-coupled receptor (Drayna, 2005). Three functional
single nucleotide polymorphisms (SNPs) within this gene
have been found to explain up to 85% of the observed vari-
ance in PTC taste sensitivity (Drayna, 2005; Kim et al., 2003).
These polymorphisms encode for amino acid substitutions
at position 49 (alanine/proline, A49P), 262 (valine/alanine,
V262A), and 296 (isoleucine/valine, I296V) (Drayna, 2005;
Kim et al., 2003). While several resulting haplotypes have
been observed, the two most common are PAV and AVI,
which correspond to the amino acids at the three positions.
PAV homozygotes exhibit the greatest sensitivity to PTC/
PROP bitterness, while AVI homozygotes are the least sen-
sitive (Bufe et al., 2005; El-Sohemy et al., 2007; Kim and
Drayna, 2004). Heterozygotes (PAV/AVI) show intermediate
bitter taste sensitivity. Interestingly, some research indicates
that TAS2R38 polymorphisms are not sufficient to explain
PROP bitterness perception at suprathreshold concentra-
tions, suggesting that other genetic or environmental mech-
anisms may also play a role in PROP taste perception (Bufe
et al., 2005; Hayes et al., 2008).
It has been hypothesized that individuals with increased
bitter taste sensitivity might avoid antioxidant-rich vegeta-
bles because of their perceived bitterness, consuming instead
sweet, fatty foods and potentially increasing their risk of car-
diovascular and other diseases. However, an increased sen-
sitivity to bitterness has also been associated with height-
ened taste acuity (Bartoshuk et al., 1994, 1998; Chang et al.,
2006; Duffy, 2004), which may prevent food overconsump-
tion in general. A number of associations have been found
between perceived PTC or PROP bitterness and food pref-
erences. For example, in young women there is an inverse
relationship between PROP sensitivity and acceptance of tart
citrus, Brassica vegetables, spinach, and coffee (Drewnowski
et al., 1998, 1999). Female PROP tasters also show a decreased
acceptance of sweet and fatty foods (Duffy and Bartoshuk,
2000).
While there seems to be an association between bitterness
sensitivity and food preferences, the potential interaction be-
tween bitterness sensitivity and actual food consumption has
yet to be fully understood. In a group of young women, per-
ceived PROP bitterness was not associated with consump-
tion frequency of 22 bitter foods (Kaminski et al., 2000). How-
ever, among men undergoing endoscopic screenings for
colon polyps, those with the highest PROP sensitivity ate
fewer vegetables (Basson et al., 2005). Interestingly, per-
ceived PROP bitterness also correlated positively with polyp
number, suggesting a possible link between PROP sensitiv-
ity and colon cancer. A similar link between increased bit-
terness sensitivity and decreased vegetable consumption
was found in an Italian population (Sacerdote et al., 2007).
AV/AV homozygotes for TAS2R38, who were considered
71
nontasters, consumed more cruciferous vegetables than in-
dividuals carrying a copy of the PA haplotype. The AV and
PA haplotypes were used as equivalent to AVI and PAV, re-
spectively.
The effects of TAS2R38 genetic variation on dietary pref-
erences and subsequent coronary heart disease (CHD) risk
were examined in postmenopausal women (Timpson et al.,
2005). No significant associations were found between geno-
type, CHD, or diet. However, the nontaster genotype,
AVI/AVI, was associated with a slightly lower risk of dia-
betes, suggesting that these women may have consumed a
more prudent diet, perhaps consisting of more bitter-tasting
vegetables, over their lifetime. No direct link was found be-
tween TAS2R38 genotype and dietary habits, but it is possi-
ble that an association between these two variables was
masked by the age of the subjects, because taste acuity is
known to diminish with age (Navarro-Allende et al., in press;
Whissell-Buechy, 1990). Interestingly, TAS2R38 taster geno-
types have been observed to associate with a preference for
sweet-tasting foods in children, but not in adults (Mennella
et al., 2005).
Other members of the T2R gene family are involved in de-
tecting bitter taste, and may influence dietary habits. For ex-
ample, a single nucleotide polymorphism in TAS2R16, which
codes for a taste receptor for bitter -glucopyranosides, has
been observed to associate with alcohol dependence (Hin-
richs et al., 2006; Wang et al., 2007). A possible link between
a polymorphism in TAS2R50 and increased risk of myocar-
dial infarction has been identified as well (Shiffman et al.,
2005, 2008). This same polymorphism might be associated
with poor dietary habits. However, no studies to date have
examined the potential relationship between TAS2R50 geno-
type and food preferences or dietary habits.
Sweet Taste
Unlike bitter taste perception, sweet substances are per-
ceived as pleasant and are clustered separately from bitter
taste in humans, possibly reflecting evolutionary pressures
to select foods high in energy (Hladik et al., 2002). It is well
established that sweet tasting substances induce cephalic-
phase reflexes, and therefore, sweet taste receptors in the
tongue and palate may be important in initiating the pre-ab-
sorptive metabolic response to food consumption (Tordoff,
1988; Zafra et al., 2006). In addition to natural sugars such
as glucose, fructose, sucrose, and sugar alcohols such as sor-
bitol, a variety of artificial sweeteners have been developed
(Knight, 1994; Mazur, 1984; Parker, 1978). Examples include
saccharin, acesulfame-K, aspartame, sucralose, and dulcin
(Boughter and Bachmanov, 2007). Additionally, amino acids
such as glycine, D-phenylalanine, D-tryptophan, L-proline,
and L-glutamine also confer a sweet taste (Boughter and
Bachmanov, 2007). However, it is not clear why organisms
have evolved to detect these nonnutritive sweeteners. De-
spite the current use of artificial sweeteners to reduce calo-
ries, there is evidence that noncaloric sweeteners may pro-
mote obesity by interfering with the normal metabolic
response to food intake (Swithers and Davidson, 2008).
Using differences in sweet taste perception of saccharin
among different strains of mice, Fuller began to pave the way
for the search to identify the Sac locus (Fuller, 1974). The dis-
covery of the gene responsible for the Sac locus was greatly
72
accelerated 25 years later after a novel G-protein coupled re-
ceptor family, TR1, was discovered in rats and humans
(Hoon et al., 1999). In 2001, several groups identified the
third member of the taste receptor family 1, T1R3 (TAS1R3
in humans, or Tas1r3 in rodents) as the gene responsible for
the saccharin preferring phenotype, which was discovered
using a number of different approaches (Bachmanov et al.,
2001; Kitagawa et al., 2001; Max et al., 2001; Montmayeur et
al., 2001; Nelson et al., 2001; Sainz et al., 2001). Direct evi-
dence for the role of Tas1r3 in saccharin preference came
from a study that isolated Tas1r3 from taster mice and res-
cued nontaster mice by transfecting them with the taster
form of the gene (Nelson et al., 2001). In addition to the
Tas1r3 gene, these studies also identified the coexpression of
T1R2 and T1R3 in circumvallate and foliate cells (Max et al.,
2001; Montmayeur et al., 2001; Nelson et al., 2001) and us-
ing a heterologous assay system, it was discovered that the
T1R2/T1R3 heteromer responded to a number of sweet sub-
stances as measured using a calcium indicator dye (Nelson
et al., 2001). It was later discovered that T1R3 in combina-
tion with T1R1 is the heteromer responsible for umami taste
detection (Nelson et al., 2002). Alpha-gustducin, which is a
G-protein coupled receptor subunit, is proposed to be one
pathway involved in transmitting the signal downstream
once the sweet taste receptor is activated by its ligand (Mar-
golskee, 2002; Sainz et al., 2007). Bitter and umami taste re-
ceptors could also transmit their signal via alpha-gustducin
(Margolskee, 2002; Sainz et al., 2007). Thus, in addition to
understanding taste receptors, understanding the down-
stream transduction pathway is key to obtaining a complete
picture of taste perception.
Despite the discovery of the T1R2/T1R3 heteromer re-
sponsible for sweet taste detection, the number of sweet taste
receptors that exist is still unresolved. Evidence from a sin-
gle and double knockout of Tas1r3 and Tas1r2 suggests that
T1R2 and/or T1R3 may act as a low affinity taste monomer
or homodimer under high concentrations of natural sugars
(Zhao et al., 2003), while another Tas1r3 knockout study sug-
gests that other sweet taste receptors might exist (Delay et
al., 2006). Interestingly, members of the Felidae family of ob-
ligate carnivores are unique because they are indifferent to
sweet tasting foods and do not show neural responses to sug-
ars (Li et al., 2005). This phenotype was explained by a mi-
crodeletion and early stop codon in the Tas1r2 gene, result-
ing in lack of T1R2 expression in taste tissue, thereby
highlighting the importance of T1R2 in sweet taste detection.
Future studies are needed to resolve the debate regarding
the number of proteins acting as a sweet taste receptor us-
ing both Tas1r3 and Tas1r2 knockouts alone and in combi-
nation.
Within humans, it has long been recognized that there are
interindividual differences in sweet taste detection thresh-
olds (Blakeslee and Salmon, 1935; Henkin and Shallenberger,
1970). A recent study of female monozygotic and dizygotic
twins reported that the additive genetic contribution to the
discrimination of the intensity of a sweet solution was 33%,
while the additive genetic contribution to liking the sweet
solution was 49% (Keskitalo et al., 2007a). The solution used
in this study was a very sweet 20% sucrose solution and,
therefore, a lower sucrose concentration may have had the
capacity to further identify interindividual differences in
sweet taste discrimination, which may have potentially ac-
GARCIA-BAILO ET AL.
counted for a greater genetic contribution to sweet taste dis-
crimination (Keskitalo et al., 2007a). Similarly, among related
and unrelated family members, heritability estimates for de-
tecting intensity of suprathreshold sucrose solutions were
near zero, yet the heritability of pleasantness of the two
strongest solutions and of sweet foods were between 30 and
40% (Keskitalo et al., 2007b). This study identified a quanti-
tative trait linkage for use frequency of sweet foods on chro-
mosome 16p11.2, but no candidate genes were identified be-
cause there are no genes known to affect sweet preference
and use in this region (Keskitalo et al., 2007b). The variabil-
ity in heritability observed in both studies, however, dem-
onstrates that preference for sweet foods is a multifactorial,
polygenic trait (Keskitalo et al., 2007a, 2007b). This is not sur-
prising given the complexity of eating behaviors, which are
influenced by other physiological systems including food re-
ward circuits and energy homeostasis in addition to differ-
ences in taste perception. We have previously demonstrated
that a genetic variant in the glucose transporter type 2
(GLUT2) gene is associated with a higher habitual con-
sumption of sugars, which suggests that glucose-sensing
mechanisms that may be involved in glucose homeostasis
and/or energy balance may affect food intake behaviours
(Eny et al., 2008). Furthermore, these different biological
pathways may converge and interact to influence the over-
all consumption of sugars. Interestingly, T1R2 and T1R3
have been localized in the small intestine and have been im-
plicated in increasing expression of GLUT2 (Mace et al., 2007)
and the sodium-dependent glucose transporter isoform 1
(SGLT1) (Margolskee et al., 2007) in the brush-border mem-
brane in response to natural and artificial sweeteners in rats
and mice (Mace et al., 2007; Margolskee et al., 2007). Thus,
examining polymorphisms within the sweet taste receptor
genes may contribute to understanding part of the differ-
ences in sweet taste detection and liking of sugars as well as
differences in postprandial glucose absorption, which may
help explain predispositions to obesity, diabetes, and other
eating disorders.
The human gene encoding T1R3, TAS1R3, is located on
chromosome 1 together with the first and second members
of the taste receptor family 1, TAS1R1 and TAS1R2, respec-
tively (Liao and Schultz, 2003). Several polymorphisms have
been identified in each of these three taste receptor genes,
which varied across the different populations studied in-
cluding Asian, Native American, African, and European
populations (Kim et al., 2006). A majority of the nonsyn-
onymous variations reside in the extracellular domain of the
protein, which is hypothesized to contain the ligand-bind-
ing site for carbohydrates and dipeptide sweeteners (Kim et
al., 2006). TAS1R2 notably had higher variation than TAS1R1
and TAS1R3, and was determined to be in the top 10th per-
centile of genetic diversity in comparison to 3305 other genes
(Kim et al., 2006). Together with the remarkable genetic di-
versity, TAS1R2 was also determined to have potentially
evolved to sense a wide variety of structurally different
sweet substances as assessed by rejecting the evolutionary
neutrality test, called Tajima’s D test (Kim et al., 2006). No
study has yet examined whether genetic variants in TAS1R2
and/or TAS1R3 are associated with differences in the con-
sumption of sugars in humans. Together with chimera stud-
ies evaluating the ligand binding and active sites of the het-
eromeric taste receptor (Nie et al., 2005; Xu et al., 2004),
GENETIC VARIATION IN TASTE
candidate polymorphisms may be investigated to begin to
understand the interindividual differences in sweet taste per-
ception and consumption of sugars.
Umami Taste
The word umami is used to describe meaty, savory flavor,
and it comes from a Japanese term meaning “good taste” or
“delicious” (Chandrashekar et al., 2006; Roper, 2007). As is
the case with sweet taste, animals are attracted to umami
taste. The main substance eliciting umami taste in humans
is L-glutamate, an amino acid abundantly found in food that
often occurs as monosodium glutamate (MSG). L-aspartate
also elicits umami taste in humans (Chandrashekar et al.,
2006; Zhao et al., 2003). The umami taste of MSG and L-as-
partate are greatly enhanced by the purine nucleotides ino-
sine 5-monophosphate (IMP) and guanosine 5-monophos-
phate (GMP) (Chandrashekar et al., 2006; Kurihara and
Kashiwayanagi, 2000; Nelson et al., 2002). Umami tastants
are found naturally in a wide array of vegetables such as
tomatoes, potatoes, mushrooms, carrots, and various sea-
weeds, as well as fish, seafood, meat, and cheese (Kurihara
and Kashiwayanagi, 2000).
Umami was first described by Ikeda in 1909. The original
description, published in Japanese, was only translated into
English in 2002 (Ikeda, 2002). Widespread acceptance of
umami as a distinct taste modality occurred slowly. This was
partly because umami substances have a subtle taste even at
high concentrations, and partly because the umami taste of
L-glutamate can be difficult to dissociate from the salty taste
of the sodium also found in MSG (Kim et al., 2004; Linde-
mann et al., 2002). However, in the past decade several
umami taste receptors have been proposed. Chaudhari et al.
(1996, 2000) first described a modified brain glutamate re-
ceptor, the metabotropic G-protein receptor taste-mGluR4,
which has a truncated N-terminus and is expressed in rat
taste buds. This receptor elicited identical behavioural re-
sponses in rats when stimulated by either MSG or L-2-amino-
4-phosphonobutyrate (L-AP4), a ligand for mGluR4 that also
elicits umami taste responses in humans. Furthermore, Chi-
nese hamster ovary cells expressing taste-mGluR4 re-
sponded to stimulation by L-AP4 and MSG in concentrations
similar to those necessary to elicit taste responses in vivo.
These results were interpreted as evidence for the role of
taste-mGluR4 in umami taste perception. However, addi-
tional evidence suggests that receptors other than taste-
mGluR4 may play a more important role in umami taste per-
ception. Most notably, the taste-mGluR4 receptor lacks a
large portion of the domain necessary for glutamate recog-
nition, and mGluR4 knockout mice still respond to umami
stimuli (Chaudhari and Roper, 1998; Zhao et al., 2003).
Umami processing seems to be closely related to sweet
taste processing at the molecular level. The 7-transmem-
brane-domain G protein-coupled receptors T1R1 and T1R3
appear to form a heteromeric umami taste receptor (Li et al.,
2002; Nelson et al., 2002; Zhao et al., 2003). The T1R1/T1R3
heteromer was first identified by expressing candidate taste
receptors in human embryonic kidney (HEK) cells and stim-
ulating them with all 20 L-amino acids, as well as several D-
amino acids that taste sweet to humans (Nelson et al., 2002).
Only cells coexpressing T1R1/T1R3 responded to L-amino
acids, and their responses were potentiated by the umami
73
enhancer IMP. Furthermore, cells transfected with human
T1R1/T1R3 responded much more strongly to glutamate, the
main human umami tastant, than cells expressing mouse
T1R1/T1R3 did. This observation was attributed to taste re-
ceptor sequence differences between the two species, per-
haps reflecting differences in their natural diets. Overall,
these results suggested a role for T1R1/T1R3 as a broad L-
amino acid receptor, which responds more specifically to
various taste stimuli depending on the animal species being
studied (Nelson et al., 2002).
Further supporting the role of T1R1/T1R3 as an umami
taste receptor, it was shown that human umami tastants
caused excitation of HEK cells only when the cells coex-
pressed human T1R1 and T1R3 (Li et al., 2002). The response
was greater in the presence of IMP or GMP, and T1R1/T1R3
did not respond to sweet stimuli, D-amino acids, or either
IMP or GMP alone. Finally, Tas1R1 and Tas1R3 knockout
mice were characterized both through behavioural tests and
by measuring activity of the gustatory chorda tympani nerve
after exposure to different taste stimuli (Zhao et al., 2003).
As expected, Tas1R1 and Tas1R3 knockout mice showed a
complete loss of preference for umami, and they exhibited
no chorda tympani nerve activity after stimulation with glu-
tamate. Thus, it seems clear that umami taste is processed
by the heteromeric T1R1/T1R3 receptor (Li et al., 2002; Nel-
son et al., 2002; Zhao et al., 2003).
To date, human umami taste perception variability re-
mains poorly understood. Individual responses of European
adults to L-glutamate were assessed through detection
threshold determination, suprathreshold evaluation, per-
ception of stimulus strength and duration, and qualitative
assessment of taste of MSG versus NaCl (Lugaz et al., 2002).
About 27% of subjects assessed were unable to distinguish
MSG from NaCl at 29 mM isomolar concentrations, mean-
ing they were unable to separate the umami taste compo-
nent from the salty component of MSG. In time-intensity
tests of MSG versus NaCl stimuli, 20% of the participants
had a weakened MSG stimulus response. These results sug-
gest a reduced ability to taste umami, but no attempt was
made to address the genetic basis of the observed MSG in-
sensitivity, and the heritability of this trait has yet to be as-
certained in family or twin studies (Kim et al., 2004).
Complete DNA sequences of the TAS1R gene family cod-
ing regions were compared across Asian, Native American,
African, and European populations (Kim et al., 2006). Sev-
eral SNPs were identified within the extracellular domain of
TAS1R1 and TAS1R3, and their frequencies varied between
populations. This evidence might suggest interindividual
variability in umami taste perception, but the relationship
between genetic polymorphisms in TAS1R1 or TAS1R3,
umami taste perception and preference for foods with this
taste has yet to be explored.
Sour Taste
Sour taste perception is generally agreed to be triggered
when acidic substances stimulate the taste buds, causing de-
polarization-induced Ca2 entry into taste receptor cells
(TRCs) (Richter et al., 2003). While slightly acidic foods are
palatable to many animals (Kim et al., 2004), most mammals
reject strong sour stimuli, and it is thought that sour taste per-
ception may help prevent the consumption of spoiled foods
74
or serve as an indicator of fruit ripeness (DeSimone et al.,
2001; Kim et al., 2004; Kinnamon and Margolskee, 1996; Lin-
demann, 2001). Sources of sour tastants include inorganic
molecules such as hydrochloric acid and organic compounds
such as acetic, citric, lactic, or tartaric acid. Normally, these
compounds are natural products of fermentation or basic
metabolic pathways such as the citric acid cycle. They can be
found in most fruits and vegetables, as well as animal prod-
ucts and man-made products such as wine (Roper, 2007).
The molecular machinery accounting for sour taste per-
ception in TRCs remained poorly understood for years. Pro-
posed mechanisms have included acid-sensing ion channels
found in rats (Ugawa et al., 1998), hyperpolarization-acti-
vated cyclic nucleotide-gated channels (Stevens et al., 2001)
and pore domain potassium ion channels (Lin et al., 2004).
In the past few years, two transient receptor potential (TRP)
ion channels have gathered strong evidence as putative sour
taste receptors (Huang et al., 2006; Ishimaru et al., 2006;
LopezJimenez et al., 2006). These two ion channels, PKD2L1
and PKD1L3, belong to the polycystic kidney disease-like
(PKDL) subfamily of TRPs, some of which act as nonselec-
tive cation channels and are permeable to both Na and
Ca2. Members of the PKD2L subfamily have a six trans-
membrane domain, as well as a pore-forming domain. The
PDK1L proteins possess 11 transmembrane spanning do-
mains, as well as large extracellular domains and short in-
tracellular carboxy domains (LopezJimenez et al., 2006).
The coexpression of PKD2L1 and PKD1L3 was first ob-
served in mouse taste cells, where it was noted that the two
molecules functioned as a heteromer and that they were ex-
pressed in a different subset of taste cells than those for
sweet, bitter, and umami (LopezJimenez et al., 2006). Subse-
quently, PKD2L1 was located to the taste pore region of taste
buds, and transfected cells expressing both PKD2L1 and
PKD1L3 were shown to respond to acids, but not to other
tastants (Ishimaru et al., 2006). Finally, mice with genetically
ablated PKD2L1-expressing cells showed a nearly complete
loss of sour taste perception, while their ability to detect
other modalities remained unchanged (Huang et al., 2006).
These results highlight the role of PKD2L1 and PKD1L3 in
sour taste perception. Nonetheless, it has been noted that,
while PKD2L1 is present in all taste cell types examined,
PKD1L3 is absent from fungiform papillae and the palate
(Huang et al., 2006; Ishimaru et al., 2006). This observation
could suggest that another, as yet unidentified molecule may
also play a role in sour taste reception.
Little is known about interindividual and interpopulation
variation in sour taste perception, and how such variation
may be linked to genetic variation. A European population
was described as having a fairly narrow unimodal distribu-
tion of sensitivity to hydrochloric, citric, acetic, and picric
acids (Blakeslee and Salmon, 1935). Existing twin studies
provide equivocal information about the role of genetics in
sour taste perception (Kaplan et al., 1967; Wise et al., 2007).
In monozygotic and fraternal twin pairs, there was little cor-
relation between absolute detection thresholds for hy-
drochloric acid and degree of relatedness, suggesting that
sour taste sensitivity was not a heritable trait (Kaplan et al.,
1967). However, by assessing the minimum concentrations
at which twins recognized the sour taste of citric and hy-
drochloric acid, rather than the absolute detection threshold,
it was found that additive genetic factors accounted for over
GARCIA-BAILO ET AL.
50% of the observed variance in sour stimulus perception
(Wise et al., 2007). This suggests a strong heritability com-
ponent of sour taste sensitivity.
Analyzing the genes for putative sour taste receptors, such
as the PKD2L1/PKD1L3 heteromer, could provide a start-
ing point to explore inter-individual variation in this trait.
Both PKD2L1 and PKD1L3 contain coding SNPs, and it is
possible that some of these polymorphisms may affect sour
taste perception, but the potential relationship between poly-
morphisms in these genes, sour taste perception, and subse-
quent food choices remains to be explored.
Salty Taste
The most abundant dietary source of salty taste is NaCl.
A number of cations such as NH4, K, and Li also elicit
salty taste responses (DeSimone and Lyall, 2006; Roper,
2007), but their taste, rather than purely salty, appears to
be associated with bitterness, sourness, or astringency
(Miyamoto et al., 2000; Roper, 2007). NaCl plays an essential
physiological role by maintaining electrolyte balance (Chan-
drashekar et al., 2006), as well as regulating blood pressure,
blood volume, and water homeostasis (Kim et al., 2004;
Roper, 2007). NaCl and salty-tasting KCl contribute Na and
K to the diet, which are ions that participate in important
physiological processes such as nerve and muscle signalling,
active transport across cell membranes, and maintaining cell
volume, pH, and cellular concentrations of other important
ions such as Ca2 (Sweeney and Klip, 2001).
While the basis of salt taste perception has been studied
for years, its molecular mechanism remains unclear. In ro-
dents, epithelial sodium channels (ENaCs) located within
taste cell membranes in fungiform papillae may play an im-
portant role in the perception of NaCl (Heck et al., 1984; Lin
et al., 1999; Schiffman et al., 1983). Given the right concen-
tration of Na in the oral cavity, Na flows passively through
these ion channels, depolarizing the TRCs, and eliciting a salt
taste response (Kim et al., 2004; Roper, 2007). ENaCs are sen-
sitive to amiloride, a diuretic drug that inhibits Na trans-
port in various epithelial tissues (Schiffman et al., 1983).
In humans, other mechanisms besides ENaCs may affect
NaCl perception. For example, the amiloride sensitivity of
NaCl perception appears to be specific to a minor sour com-
ponent of this taste, rather than to the salty stimulus itself
(Ossebaard and Smith, 1995). Furthermore, salty taste per-
ception is inhibited in subjects that rinse with the oral anti-
septic chlorhexidine, suggesting that salt-sensitive ion chan-
nels in TRCs are not specifically sensitive to amiloride
(Breslin and Tharp, 2001).
An amiloride-insensitive vanilloid receptor, Trpv1, has
been proposed to play a role in salty taste perception in ro-
dents (Lyall et al., 2004). This taste receptor has been hy-
pothesized to respond to various cations, including Na, K,
NH4, and Ca2 (DeSimone and Lyall, 2006). However, the
importance of this protein has been questioned because
knockout mice lacking the receptor are nonetheless respon-
sive to salt taste (Ruiz et al., 2006). In absolute threshold de-
tection tests, Trpv1 knockout and wild-type mice detected
NaCl, as well as KCl, at similar concentrations. The mice were
also given preference tests of NaCl versus water, and of KCl
versus water. In both types of test, the Trpv1 knockout mice
actually preferred the salty tasting solution over water com-
GENETIC VARIATION IN TASTE 75

pared to wild-type animals. As these results suggest, the role
of Trpv1 in salty taste perception is unclear, but there seems
to be agreement over the fact that salty taste is mediated by
ion flow, and both amiloride-sensitive and amiloride-insen-
sitive sodium channels are involved in some capacity.
Genetic variation may affect salty taste perception in ro-
dents, and different laboratory strains of mice and rats have
been observed to respond differently to NaCl and amiloride
(Doolin and Gilbertson, 1996; Formaker and Hill, 1991; Ni-
nomiya et al., 1984a, 1984b). An SNP within the Scnn1a (so-
dium channel, nonvoltage gated, type 1 ) gene, which en-
codes for the  ENaC subunit, has been linked to this
difference in response to NaCl and amiloride (Shigemura et
al., 2008). This SNP (C1877T) results in an arginine to tryp-
tophan substitution (R616W) in the  subunit protein.
Amiloride inhibits responses to NaCl more strongly in mice
carrying a copy of the arginine-coding allele than in mice ho-
mozygous for the tryptophan-coding allele (Shigemura et al.,
2008). These results suggest that the R616W substitution in
the  ENaC subunit affects amiloride sensitivity of the ENaC
channel, and may in turn affect salty taste responses in mice.
In humans, variability in responses to salty stimuli has
been examined for decades, but a direct genetic link to hu-
man salt taste perception has yet to be uncovered. A narrow,
unimodal distribution of sensitivity to NaCl and KCl was
observed in a small sample of European subjects (Blakeslee
and Salmon, 1935). However, an African population showed
a bimodal distribution of salty taste sensitivity (Odeigah,
1994). While this may indicate a heritability component, en-
vironmental exposure to NaCl probably plays an important
role in observed salty taste perception variability (Crystal
and Bernstein, 1995; Pittman and Contreras, 2002; Stein et
al., 1996; Wise et al., 2007). Furthermore, as evidenced by
twin studies, salty taste perception appears to be determined
more by environment than by heritability components
(Beauchamp, et al., 1985; Wise et al., 2007). Given the essen-
tial role of NaCl in physiological processes, it is possible that
evolutionary forces may have shaped the human ability to
taste salt so as to be strongly influenced by environmental
and dietary cues (Wise et al., 2007).
“Fat Taste”
From an evolutionary perspective, “fat taste” perception
may have evolved to detect high energy foods and to select
foods containing fat soluble vitamins and essential fatty acids
(FAs) (Laugerette et al., 2007). Physiologically, fat detection
in the cephalic phase may aid in preparing the digestive sys-
tem for lipid metabolism. Indeed, in feeding trials an oral fat
stimulus triggers a rapid increase in plasma triacylglycerol,
implicating incoming oral fat in the release of stored fat
(Mattes, 2002). It is well known that in free choice scenarios
there is a natural tendency toward fat consumption. Both rats
and mice select a high fat diet over a low-fat diet (Hamilton,
1964) and humans may have a comparable inclination to-
ward dietary fat (Mela and Sacchetti, 1991). The mechanisms
guiding fat detection have traditionally been attributed to
texture and olfaction. However, blocking the ability to sense
these factors fails to abolish the recognition of dietary fat sug-
gesting another mechanism also contributes (Fukuwatari et
al., 2003; Takeda et al., 2001). Our ability to detect trace
amounts of FAs, including oleic, stearic, and linoleic FAs, on
the tongue indicates that their oral detection may be another
cue (Chale-Rush et al., 2007).
Some of the early evidence for a “fat taste” receptor came
from observations that FAs inhibit delayed rectifying K
channels on TRC, prolonging cell depolarization (Gilbertson
et al., 1997). The response appeared to be specific to unsat-
urated long-chain fatty acids (LCFAs) and was generally
limited to stimuli applied extracellularly, consistent with an
apical taste receptor. One good candidate for a “fat taste” re-
ceptor is CD36, which Laugerette et al. (2005) have recently

FIG. 2. With the discovery of the putative taste receptors for the different taste modalities (bitter, sweet, umami, sour,
salty, and fat), we can begin to examine genetic variation leading to differences in taste perception. The identification of ge-
netic polymorphisms associated with differences in taste perception will allow for functionality studies to determine phe-
notypic outcomes and assess their impact on food selection. Food selection results from the balance between taste percep-
tion and other factors, including nutritional status, physiology, environment, and sociocultural factors.
76 GARCIA-BAILO ET AL.

proposed to be an oral lipid sensor. CD36 is an integral mem- Discussion and Conclusion
brane protein that has a high affinity for LCFA (Baillie et al.,
The characterization of taste receptor genes, together with
1996) and is generally known for its role in facilitating free
the development of genomic technologies, has generated
fatty acid (FFA) transport across the cell membrane (Harmon
new avenues of research on the physiology of taste in hu-
and Abumrad, 1993). However, some controversy surrounds
mans. Different approaches can be used to determine how
this role (Hamilton, 2007). CD36 was isolated on the apical
variations in taste receptor genes influence taste perception,
surface of taste bud cells the same year as the K channel
food choices, and dietary intake behaviors. Understanding
TRC studies (Fukuwatari et al., 1997). The protein spans the
this relationship requires distinguishing actual dietary in-
cell membrane creating a large extracellular hydrophobic
take from food preferences. Using different methods of di-
loop, likely the portion that interacts with FAs, and two short
etary assessment such as food frequency questionnaires,
cytoplasmic tails (Abumrad et al., 1993). Although this pro-
food diaries, and food preference checklists can help estab-
tein structure expressed on taste buds supports an apical
lish the validity and reliability of genetic markers of dietary
taste receptor, the precise mechanism by which the protein
intake. Threshold studies that incorporate genotype may
senses FAs is not clear. The sensing ability appears to be spe-
help characterize the functionality of specific polymor-
cific to longer chain FAs, but both saturated and unsaturated
phisms as either having a low detection threshold or induc-
LCFA can cause depolarizing increases in intracellular cal-
ing a supertasting phenotype for a particular taste modal-
cium in CD36-positive cells. Moreover, a CD36-specific in-
ity. Because other biological factors are involved in food
hibitor, sulfo-N-succinimidyl oleic acid ester, attenuates this
selection, future studies should examine how taste percep-
response (Gaillard et al., 2008). In addition to being ex-
tion interacts with energy homeostatic pathways and food
pressed on the tongue, CD36 is also expressed in the stom-
reward circuits for a comprehensive understanding of in-
ach and intestine and on the surface of macrophages,
gestive behavior. It is also important to consider how non-
adipocytes, muscle cells, endothelial cells, and platelets.
genetic aspects such as environment and sociocultural fac-
Direct evidence demonstrating that CD36 may act as a pu-
tors influence food selection. The contributions from each
tative “fat taste” receptor comes from animal studies using
of these variables determine overall ingestive behavior, with
knockout mice (Laugerette et al., 2005). Unlike wild-type mice
the potential for nongenetic factors to override genetic pre-
that normally choose a FFA containing diet over control, mice
disposition (Fig. 2).
with a targeted deletion of the CD36 gene lose the ability to
Genetic and environmental factors contribute to nutri-
distinguish between the two (Laugerette et al., 2005). These
tional and overall health status, which are both growing pub-
observations appear to be specific for fat, as opposed to a gen-
lic health concerns. Understanding food intake behaviors
eral loss of taste, as indicated by the maintenance of a pref-
from the perspective of taste perception is important because
erence for sweet and aversion for bitter (Laugerette et al.,
it lies at the interface between the foods an individual is ex-
2005). Although dietary fat is predominantly in the form of
posed to and the biological predisposition to prefer certain
triglycerides, lingual lipase may yield sufficient FFA to act as
foods in one’s environment. Examining variations in taste re-
a chemical cue. Kawai and Fushiki (2003) showed that inhi-
ceptors will help establish the association between certain
bition of lingual lipase reduced the intake of triglyceride, but
food intake behaviors and risk of chronic disease. Polymor-
failed to reduce the intake of FFA. Indeed, lipase secretion is
phisms in taste receptors might be useful as surrogate mark-
constant and yields FFAs quickly enough to enable them to
ers of dietary exposure in gene–disease association studies
be detected by a fat sensor on the surface of the tongue (Kawai
where information on dietary habits is not available. In ad-
and Fushiki, 2003). A more recent study confirmed that com-
dition, differences in genetic variation in taste receptors be-
pared to lipid naïve CD36-null mice, wild-type mice are more
tween ethnic groups may contribute to differences in dietary
likely to choose a FA solution over gum vehicle (0.3% xan-
intake patterns. Understanding these differences in genetic
than gum), indicating that CD36 is required to distinguish
variation could help explain the interethnic disparities in risk
these texturally comparable choices (Sclafani et al., 2007) .
for chronic disease and lead to the development of appro-
These CD36-null mice also showed a weaker preference for
priate preventative public health measures.
triglyceride over Emplex vehicle (0.15% sodium stearoyl
lactylate) than their wild-type littermates (Sclafani et al.,
Acknowledgments
2007). However, at increasing concentrations of both FA and
triglyceride CD36-null mice exhibited increased fat prefer- This work was supported by a grant from the Advanced
ences, although their total fat intake continued to be less than Foods & Materials Network (AFMNet). A. El-Sohemy holds
that of their wild-type littermates. The authors suggest that a Canada Research Chair in Nutrigenomics.
postoral conditioning effects may in part be responsible for
this “rescued” phenotype (Sclafani et al., 2007). Author Disclosure Statement
The role of CD36 in mediating fat intake in humans is not
yet known. A number of sequence variations in the human The authors declare that no competing financial interests
CD36 gene, located on chromosome 7q11.2, have been iden- exist.
tified (Fernandez-Ruiz et al., 1993). If genetic variation in
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Address reprint requests to:
Dr. Ahmed El-Sohemy
Department of Nutritional Sciences
Faculty of Medicine
University of Toronto
150 College Street
Toronto, Ontario, M5S 3E2, Canada
E-mail: a.el.sohemy@utoronto.ca