Bitter Receptor Genes Research Articles

Genomic and functional insights into dietary diversification in New World leaf‐nosed bats (Phyllostomidae)

AbstractThe most significant driver of adaptive radiation in the New World leaf‐nosed bats (Phyllostomidae) is their remarkably diverse feeding habits, yet there remains a notable scarcity of studies addressing the genetic underpinnings of dietary diversification in this family. In this study, we have assembled a new genome for a representative species of phyllostomid bat, the fringe‐lipped bat (Trachops cirrhosis), and integrated it with eight published phyllostomid genomes, along with an additional 10 genomes of other bat species. Comparative genomic analysis across 10 200 orthologus genes has unveiled that those genes subject to divergent selection within the Phyllostomidae clade are notably enriched in metabolism‐related pathways. Furthermore, we identified molecular signatures of divergent selection in the bitter receptor gene Tas2r1, as well as 14 genes involved in digesting key nutrients such as carbohydrates, proteins, and fats. In addition, our cell‐based functional assays conducted on Tas2r1 showed a broader spectrum of perception for bitter compounds in phyllostomids compared to nonphyllostomid bats, suggesting functional diversification of bitter taste in Phyllostomidae. Together, our genomic and functional analyses lead us to propose that divergent selection of genes associated with taste, digestion and absorption, and metabolism assumes a pivotal role in steering the extreme dietary diversification in Phyllostomidae. This study not only illuminates the genetic mechanisms underlying dietary adaptations in Phyllostomidae bats but also enhances our understanding of their extraordinary adaptive radiation.

Oral CD8 +T RMsurveil taste buds where their local reactivation drives papillary inflammation and bitter receptor expression

Abstract Resident memory T cells (T RM) expedite pathogen detection and clearance at typical portals of pathogen entry. While paradigms in T RMbiology were largely established in a few select locations, comparatively little is known about how CD8 +T RMintegrate within the oral cavity, which encompasses a functionally organized constellation of absorptive, secretory, and chemosensory tissues. To fill this knowledge gap, we developed a Viral-Prime, Epitope-Pull (VPEP) model for locally augmenting tractable populations of oral T RMto manipulate and study. Leveraging this approach, we document CD8 +T RMwithin and surrounding taste buds and papillae of the soft palate and tongue. Reactivation of oral T cells induced discernable inflammation within taste structures that was abrogated with prior in vivoCD103 +T RMdepletion. Taste buds represent a collection of ~50–100 individual taste receptor cells (TRCs) which sense nutritive and potentially harmful dietary components. We hypothesized that reactivation of taste bud associated T RMwould provoke TRC transcriptional changes including genes involved in gustation (taste). Bulk RNAseq was performed on T RM-reactivated circumvallate papillae and soft palate; primary taste-sensing locations in mice and enriched sources of TRCs relative to other oral tissues. Here we found the significant induction of several Tas2r(bitter receptor) genes not observed in control mice or T RMreactivated buccal mucosa. Teleologically, a heightened sensitivity to bitter compounds downstream of oral T RMreactivation may represent an evolved mechanism to protect against the accidental ingestion of noxious chemicals during oral or upper respiratory tract infections when other chemosensory modalities faulter. T90 DE 022732 K99DE031014

TAS1R3 and TAS2R38 Polymorphisms Affect Sweet Taste Perception: An Observational Study on Healthy and Obese Subjects.

Background: The inter-individual differences in taste perception find a possible rationale in genetic variations. We verified whether the presence of four different single nucleotide polymorphisms (SNPs) in genes encoding for bitter (TAS2R38; 145G > C; 785T > C) and sweet (TAS1R3; −1572C > T; −1266C > T) taste receptors influenced the recognition of the basic tastes. Furthermore, we tested if the allelic distribution of such SNPs varied according to BMI and whether the associations between SNPs and taste recognition were influenced by the presence of overweight/obesity. Methods: DNA of 85 overweight/obese patients and 57 normal weight volunteers was used to investigate the SNPs. For the taste test, filter paper strips were applied. Each of the basic tastes (sweet, sour, salty, bitter) plus pure rapeseed oil, and water were tested. Results: Individuals carrying the AV/AV diplotype of the TAS2R38 gene (A49P G/G and V262 T/T) were less sensitive to sweet taste recognition. These alterations remained significant after adjustment for gender and BMI. Moreover, a significant decrease in overall taste recognition associated with BMI and age was found. There was no significant difference in allelic distribution for the investigated polymorphisms between normal and overweight/obese patients. Conclusions: Our findings suggest that overall taste recognition depends on age and BMI. In the total population, the inter-individual ability to identify the sweet taste at different concentrations was related to the presence of at least one genetic variant for the bitter receptor gene but not to the BMI.

Are taste variations associated with the liking of sweetened and unsweetened coffee?

ObjectiveIn this study, we evaluated the influence of taste phenotypes and genotypes on the hedonics of sweetened and unsweetened coffee. MethodsLiking of espresso coffee from food questionnaire and of a ready-to-drink unsweetened coffee beverage was measured using a 9-point hedonic scale in 1551 Italian individuals. Perception and liking for different bitter and sweet compounds were also collected. Genotyping of selected Single Nucleotide Polymorphisms (SNPs) in five taste genes (TAS1R3, GNAT3, TAS2R14, TAS2R19, TAS2R38) was performed. Linear and logistic regression models, including sex and gender as covariates, were used to test the relationship of taste phenotypes and selected SNPs with coffee liking. ResultsWe found that increased caffeine bitterness perception was associated with an increasing liking for sweetened coffee (p-value = 0.018) and decreased liking of unsweetened coffee (p-value = 0.034). The liking of unsweetened coffee beverage was also negatively associated with sweet intensity perception (p-value = 0.03). Analysis of SNPs in taste-related genes showed that rs6467192 G allele (intron 4 variant) in GNAT3 sweet taste gene was associated with higher liking of sweetened coffee (p-value = 0.002) and lower liking of unsweetened coffee (p-value = 0.01). An association also emerged between unsweetened coffee and SNPs in bitter receptor genes, with rs2597979 in TAS2R14 gene associated with liking of unsweetened coffee (p-value = 0.004) and rs10772420 in TAS2R19 gene associated with liking of both unsweetened espresso coffee and coffee beverage (p-value = 0.04 and p-value = 0.03, respectively). ConclusionThese findings suggested that individual preference for sweetened and unsweetened coffee may be influenced by both phenotypic and nucleotide variations in bitter and sweet taste sensitivity.

The genome of the black cutworm Agrotis ipsilon

The black cutworm (BCW), Agrotis ipsilon, is a worldwide polyphagous and underground pest that causes a high level of economic loss to a wide range of crops through the damage of roots. This species performs non-directed migration throughout East and Southeast Asia seasonally. Lack of a genome information has limited further studies on its unique biology and the development of novel management approaches. In this study, we present a 476 Mb de novo assembly of BCW, along with a consensus gene set of 14,801 protein-coding gene models. Quality controls show that both genome assembly and annotations are high-quality and mostly complete. We focus manual annotation and comparative genomics on gene families that related to the unique attributes of this species, such as nocturnality, long-distance migration, and host adaptation. We find that the BCW genome encodes a similar gene repertoire in various migration-related gene families to the diural migratory butterfly Danaus plexiipus, with additional copies of long wavelength opsin and two eye development-related genes. On the other hand, we find that the genomes of BCW and many other polyphagous lepidopterans encode many more gustatory receptor genes, particularly the lineage-specific expanded bitter receptor genes, than the mono- or oligo-phagous species, suggesting a common role of gustatory receptors (GRs) expansion in host range expansion. The availability of a BCW genome provides valuable resources to study the molecular mechanisms of non-directed migration in lepidopteran pests and to develop novel strategies to control migratory nocturnal pests.

Genetic preferences for food

Genetic preferences for food

Taste receptors in aquatic mammals: Potential role of solitary chemosensory cells in immune responses.

The sense of taste is associated with the evaluation of food and other environmental parameters such as salinity. In aquatic mammals, anatomic and behavioral evidence of the use of taste varies by species and genomic analysis of taste receptors indicates an overall reduction and, in some cases, complete loss of intact bitter and sweet taste receptors. However, the receptors used by taste buds in the oral cavity are found on cells in other areas of the body and play an important role in immune responses. In the respiratory tract, an example of such cells is solitary chemosensory cells (SCCs) which have bitter and sweet taste receptors. The bitter receptors detect chemicals given off by pathogens and initiate an innate immune response. Although many aquatic mammals may not have a role for taste in the assessment of food, they likely would benefit from the added protection that SCCs provide, especially considering respiratory diseases are a problem for many aquatic mammals. While evidence indicates that some species do not possess functional bitter receptors for taste, many do have intact bitter receptor genes and it is important for researchers to be aware of all roles for these receptors in homeostasis. Through a better understanding of the anatomy and physiology of aquatic mammal's respiratory systems, better treatment and management is possible.

Tissue-Dependent Expression of Bitter Receptor TAS2R38 mRNA.

TAS2R38 is a human bitter receptor gene with a common but inactive allele; people homozygous for the inactive form cannot perceive low concentrations of certain bitter compounds. The frequency of the inactive and active forms of this receptor is nearly equal in many human populations, and heterozygotes with 1 copy of the active form and 1 copy of the inactive form have the most common diplotype. However, even though they have the same genotype, heterozygotes differ markedly in their perception of bitterness, perhaps in part because of differences in TAS2R38 mRNA expression. Other tissues express this receptor too, including the nasal sinuses, where it contributes to pathogen defense. We, therefore, wondered whether heterozygous people had a similar wide range of TAS2R38 mRNA in sinonasal tissue and whether those with higher TAS2R38 mRNA expression in taste tissue were similarly high expressers in nasal tissue. To that end, we measured gene expression by quantitative PCR in taste and sinonasal tissue and found that expression abundance in one tissue was not related to the other. We confirmed the independence of expression in other tissue pairs expressing TAS2R38 mRNA, such as pancreas and small intestine, using autopsy data from the Genotype-Tissue Expression project (although people with high expression of TAS2R38 mRNA in colon also tended to have higher expression in the small intestine). Thus, taste tissue TAS2R38 mRNA expression among heterozygotes is unlikely to predict expression in other tissues, perhaps reflecting tissue-dependent function, and hence regulation, of this protein.

Personalized expression of bitter 'taste' receptors in human skin.

The integumentary (i.e., skin) and gustatory systems both function to protect the human body and are a first point of contact with poisons and pathogens. These systems may share a similar protective mechanism because, as we show here, both human taste and skin cells express mRNA for bitter ‘taste’ receptors (TAS2Rs). We used gene-specific methods to measure mRNA from all known bitter receptor genes in adult human skin from freshly biopsied samples and from samples collected at autopsy from the Genotype-Tissue Expression project. Human skin expressed some but not all TAS2Rs, and for those that were expressed, the relative amounts differed markedly among individuals. For some TAS2Rs, mRNA abundance was related to presumed sun exposure based on the location from which the skin sample was collected (TAS2R14, TAS2R30, TAS2R42, and TAS2R60), sex (TAS2R3, TAS2R4, TAS2R8, TAS2R9, TAS2R14, and TAS2R60), and age (TAS2R5), although these effects were not large. These findings contribute to our understanding of extraoral expression of chemosensory receptors.

Taste Perception of Antidesma bunius Fruit and Its Relationships to Bitter Taste Receptor Gene Haplotypes.

It was shown more than 40 years ago that the ability to perceive the bitterness of the fruit of the Antidesma bunius tree is inversely correlated with the ability to perceive the well-studied bitter tastant phenylthiocarbamide (PTC). To determine if variants of the TAS2R38 gene, which encodes the PTC taste receptor, or variants in any of the other TAS2R bitter or TAS1R sweet receptor genes account for Antidesma taste perception, we recruited an independent subject sample and examined associations between these taste receptor gene haplotypes and Antidesma perception. Consistent with previous findings, almost none of our subjects who reported Antidesma juice as bitter was a PTC "responder" by previous definitions (i.e. a PTC taster). In our study, of the 132 individuals who perceived PTC as bitter, 15 perceived Antidesma as bitter, although these 15 subjects had very weak bitterness perception scores. Examination of TAS2R38 gene haplotypes showed that, of the subjects who perceive Antidesma as bitter, all carried at least one copy of the TAS2R38 AVI (PTC non-taster) haplotype. However, 86 subjects carried at least one AVI haplotype and failed to perceive Antidesma as bitter. No other TAS2R or TAS1R gene variants showed an association with Antidesma bitter, sweet, or sour perception. Our results show that TAS2R38 haplotypes are associated with differential perception of Antidesma berry juice bitterness, and that all those who perceive this bitterness carry at least one AVI haplotype. This indicates that the AVI haplotype is necessary for this perception, but that additional variable factors are involved.

Research progress of the bitter taste receptor genes in primates.

Among the five basic tastes (umami, sweet, bitter, salty and sour), the perception of bitterness is believed to protect animals from digesting toxic and harmful substances, thus it is vital for animal survival. The taste of bitterness is triggered by the interaction between bitter substances and bitter taste receptors, which are encoded by Tas2rs. The gene numbers vary largely across species to meet different demands. So far, several ligands of bitter receptors have been identified in primates. They also discovered that the selective pressure of certain bitter taste receptor genes vary across taxa, genes or even different functional regions of the gene. In this review, we summarize the research progress of bitter taste receptor genes in primates by introducing the functional diversity of bitter receptors, the specific interaction between bitter taste receptors and ligands, the relationship between the evolutionary pattern of bitter taste receptors and diets, and the adaptive evolution of bitter taste receptor genes. We aim to provide a reference for further research on bitter receptor genes in primates.

Use of Adult Sensory Panel to Study Individual Differences in the Palatability of a Pediatric HIV Treatment Drug

PurposeThe recommended first-line treatment for young children infected with HIV includes the liquid formulation of the co-formulated protease inhibitors lopinavir/ritonavir (Kaletra® [Abbott Laboratories, Chicago, Illinois]). Clinical reports indicate that some children readily accept the taste of Kaletra, whereas others strongly reject it, which can deter therapeutic adherence and outcomes. MethodsAs a proof-of-concept approach, a sensory panel of genotyped adults was used to document the range of individual differences in the taste and palatability (hedonics) of the liquid formulation of Kaletra and other taste stimuli, including common excipients. Panelists rated taste sensations using generalized labeled magnitude scales to determine genotype–phenotype relationships. Several months later, the panelists were retested to assess response reliability. FindingsNot all panelists had the same sensory experience when tasting Kaletra. Palatability ratings varied widely, from moderate like to strongest imaginable dislike, and were reliable over time. The more irritating and bitter Kaletra tasted, the more disliked by the panelist. The more they disliked the taste of Kaletra, the more they disliked the taste of its excipient ethanol and the bitter stimulus denatonium. Those who experienced less bitter and sweeter taste sensations had a different genetic signature than the other panelists. Bitterness and irritation ratings of Kaletra varied by the orphaned bitter receptor gene (TAS2R60), whereas sweetness ratings of Kaletra varied according to the cold receptor gene (TRPM8), which is activated by menthol, an excipient of Kaletra. Neither genotype related to ratings for ethanol or denatonium, however. ImplicationsThe use of a sensory panel holds promise as a first step in determining the nature of individual differences in the palatability of existing pediatric drug formulations and sources of variation. In this era of personalized medicine, the need is great to develop psychophysical tools to determine which drugs will show variation in acceptance by children and whether patterns of individual variation in taste as assessed by adults mirror those of young patients. ClinicalTrials.gov identifier: NCT01841710.

Suprathreshold measures of taste perception in children - Association with dietary quality and body weight

Childhood obesity is an increasing problem in the Western world, and is affected by a multitude of interacting factors. Recent evidence suggests that taste perception may differ between obese and normal weight children. Evidence also suggests that perception of sweet and bitter taste is linked to differential food liking of various foods. To date, most studies have focused on single food items or food groups, rather than an overall view of dietary quality, and mainly on bitterness. Thus it is unclear whether taste perception is associated with dietary quality in children. Our objective was to examine the link between taste perception, dietary quality and body weight in Irish school children, in conjunction with other known influences of body weight. Taste perception was measured using the gLMS for bitter, salty and sweet stimuli. Detailed dietary intake data were collected from 525 children aged 7–13 via a 3-day diet history. Energy misreporters were identified and excluded from the dietary analyses, leaving n = 483 children. Dietary quality was assessed using Healthy Eating Index. Salivary DNA was collected and analyzed for variations in the bitter receptor gene TAS2R38. Sex differences were observed whereby intensity perception of sweetness was lower in the overweight/obese males, while no association was observed for sweet taste in the females. Despite the differences in weight status, taste perception was not associated with differences in overall dietary quality, measured via HEI score, in this cohort. Prospective cohort studies in children are necessary to better understand the association between taste intensity, food intake and weight over time.

Association of TAS2R38 variants with sweet food intake in children aged 1–6 years

We aimed at studying whether genetic variants of the TAS2R38 gene are associated with energy intake from sweet tasting foods, total energy and macronutrient intake and body weight in children.Children (n = 691) from five European countries were genotyped for the first variant site rs713598 of the TAS2R38 bitter receptor gene. Three-day dietary records were obtained yearly from one to six years of age. Foods were categorized in sweet and non-sweet-tasting. Mixed models were used to describe group differences in food and nutrient intake and BMI z-score over time.TAS2R38 genotype was related to energy intake from sweet tasting foods: Children with PP and PA genotype consumed an average 83 kJ/d (95% CI 21 to 146; p = 0.009) more sweet tasting foods than children with AA genotype and a mean 56 kJ/d (95% CI 15 to 98; p = 0.007) more energy from energy dense sweet products. Intake of sweet tasting foods was lower in girls than boys and differed between countries. TAS2R38 genotype was not associated with the intake of energy, macronutrients, sugar, single food groups and BMI z-score.Despite many other factors influencing food preference and intake in children, actual intake of sweet food items is associated with TAS2R38 genotype. Children with PP or PA genotype consume more (energy dense) sweet tasting foods.

Comprehensive Analysis of Mouse Bitter Taste Receptors Reveals Different Molecular Receptive Ranges for Orthologous Receptors in Mice and Humans

One key to animal survival is the detection and avoidance of potentially harmful compounds by their bitter taste. Variable numbers of taste 2 receptor genes expressed in the gustatory end organs enable bony vertebrates (Euteleostomi) to recognize numerous bitter chemicals. It is believed that the receptive ranges of bitter taste receptor repertoires match the profiles of bitter chemicals that the species encounter in their diets. Human and mouse genomes contain pairs of orthologous bitter receptor genes that have been conserved throughout evolution. Moreover, expansions in both lineages generated species-specific sets of bitter taste receptor genes. It is assumed that the orthologous bitter taste receptor genes mediate the recognition of bitter toxins relevant for both species, whereas the lineage-specific receptors enable the detection of substances differently encountered by mice and humans. By challenging 34 mouse bitter taste receptors with 128 prototypical bitter substances in a heterologous expression system, we identified cognate compounds for 21 receptors, 19 of which were previously orphan receptors. We have demonstrated that mouse taste 2 receptors, like their human counterparts, vary greatly in their breadth of tuning, ranging from very broadly to extremely narrowly tuned receptors. However, when compared with humans, mice possess fewer broadly tuned receptors and an elevated number of narrowly tuned receptors, supporting the idea that a large receptor repertoire is the basis for the evolution of specialized receptors. Moreover, we have demonstrated that sequence-orthologous bitter taste receptors have distinct agonist profiles. Species-specific gene expansions have enabled further diversification of bitter substance recognition spectra.

Individual Differences Among Children in Sucrose Detection Thresholds: Relationship With Age, Gender, and Bitter Taste Genotype.

BackgroundLittle research has focused on whether there are individual differences among children in their sensitivity to sweet taste and, if so, the biological correlates of such differences.ObjectivesOur goal was to understand how variations in children’s sucrose detection thresholds relate to their age and gender, taste genotype, body composition, and dietary intake of added sugars.MethodsSucrose detection thresholds in 7- to 14-year-old children were tested individually using a validated, two-alternative, forced-choice, paired-comparison tracking method. Five genetic variants of taste genes were assayed: TAS1R3 and GNAT3 (sweet genes; one variant each) and the bitter receptor gene TAS2R38 (three variants). All children were measured for body weight and height. A subset of these children were measured for the percentage of body fat and waist circumference and provided added sugar intake by 24-hour dietary recall.ResultsSucrose thresholds ranged from 0.23 to 153.8 mM with most of the children completing the threshold task (216/235; 92%). Some children were biologically related (i.e., siblings), and for the genetic analysis, one sibling from each family was studied. Variants in the bitter but not the sweet genes were related to sucrose threshold and sugar intake; children with two bitter-sensitive alleles could detect sucrose at lower concentrations (F(2,165) = 4.55, p = .01; rs1726866) and reported eating more added sugar (% kcal; F(2, 62) = 3.64, p = .03) than did children with less sensitive alleles. Age, gender, and indices of obesity also were related to child-to-child differences in sucrose threshold; girls were more sensitive than boys (t(214) = 2.0, p = .05), older children were more sensitive than younger children (r(214) = −.16, p = .02), and fatter (r(84) = −.22, p = .05) or more centrally obese children (r(84) = −.26, p = .02) were more sensitive relative to others.DiscussionInborn differences in bitter sensitivity may affect childhood dietary sugar intake with long-term health consequences. There may be a more complex interplay between the developing bitter and sweet taste systems than previously understood.

Functional Analyses of Bitter Taste Receptors in Domestic Cats (Felis catus).

Cats are obligate carnivores and under most circumstances eat only animal products. Owing to the pseudogenization of one of two subunits of the sweet receptor gene, they are indifferent to sweeteners, presumably having no need to detect plant-based sugars in their diet. Following this reasoning and a recent report of a positive correlation between the proportion of dietary plants and the number of Tas2r (bitter receptor) genes in vertebrate species, we tested the hypothesis that if bitter perception exists primarily to protect animals from poisonous plant compounds, the genome of the domestic cat (Felis catus) should have lost functional bitter receptors and they should also have reduced bitter receptor function. To test functionality of cat bitter receptors, we expressed cat Tas2R receptors in cell-based assays. We found that they have at least 7 functional receptors with distinct receptive ranges, showing many similarities, along with some differences, with human bitter receptors. To provide a comparative perspective, we compared the cat repertoire of intact receptors with those of a restricted number of members of the order Carnivora, with a range of dietary habits as reported in the literature. The numbers of functional bitter receptors in the terrestrial Carnivora we examined, including omnivorous and herbivorous species, were roughly comparable to that of cats thereby providing no strong support for the hypothesis that a strict meat diet influences bitter receptor number or function. Maintenance of bitter receptor function in terrestrial obligate carnivores may be due to the presence of bitter compounds in vertebrate and invertebrate prey, to the necessary role these receptors play in non-oral perception, or to other unknown factors. We also found that the two aquatic Carnivora species examined had fewer intact bitter receptors. Further comparative studies of factors driving numbers and functions of bitter taste receptors will aid in understanding the forces shaping their repertoire.

Multiple loss-of-function variants of taste receptors in modern humans.

Despite recent advances in the knowledge of interindividual taste differences, the underlying genetic backgrounds have remained to be fully elucidated. Much of the taste variation among different mammalian species can be explained by pseudogenization of taste receptors. Here I investigated whether the most recent disruptions of taste receptor genes segregate with their intact forms in modern humans by analyzing 14 ethnically diverse populations. The results revealed an unprecedented prevalence of 25 segregating loss-of-function (LoF) taste receptor variants, identifying one of the most pronounced cases of functional population diversity in the human genome. LoF variant frequency in taste receptors (2.10%) was considerably higher than the overall LoF frequency in human genome (0.16%). In particular, molecular evolutionary rates of candidate sour (14.7%) and bitter (1.8%) receptors were far higher in humans than those of sweet (0.02%), salty (0.05%), and umami (0.17%) receptors compared with other carnivorous mammals, although not all of the taste receptors were identified. Many LoF variants are population-specific, some of which arose even after population differentiation, not before divergence of the modern and archaic human. I conclude that modern humans might have been losing some sour and bitter receptor genes because of high-frequency LoF variants.

Quinine Bitterness and Grapefruit Liking Associate with Allelic Variants in TAS2R31.

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.

Bitter taste and nicotine preference: evidence for sex differences in rats

Background: Nicotine affects sensory pathways and an interaction between taste and nicotine preference is likely. In addition to pharmacologic effects, orosensory factors are important in nicotine dependence. Recent evidence suggests a link between taste (notably bitter) receptor genes and nicotine addiction. Objectives: To explore the possible interaction between taste and nicotine preference in rats, including sex as a factor. Methods: Adult male and female Sprague Dawley rats (n = 82) were used in free choice oral intake experiments. In Experiment 1 rats received water from one bottle and one of the taste substances (quinine, sucrose, or saccharine) from the other bottle for 12 days. Following a wash-out period, Experiment 2a was initiated in the same rats. Rats received water from one bottle and nicotine (10 and 20 mg/l) from the other for 12 days. In Experiment 2b, nicotine exposure was continued for four more weeks. Liquid intake and weight were measured at four-day (Experiments 1 and 2a) and one week (Experiment 2b) periods. Results: In female rats, quinine and subsequent nicotine intake were positively correlated and quinine intake and weight gain were negatively correlated. No association was depicted between nicotine consumption and sweet tastants in either female or male animals. Conclusion: The results suggest that bitter taste and nicotine preference are related, but only in female rats. This finding is parallel to observations in human smokers. Our study may be a preliminary step in the search for common genes that underlie nicotine dependence and taste preference.