Variation in the gene TAS2R38 is associated with the eating behavior disinhibition in Old Order Amish women.
ABSTRACT: Insensitivity to the bitter-tasting compound 6-n-propylthiouracil (PROP) has been proposed as a marker for individual differences in taste perception that influence food preference and intake. The principal genetic determinants of phenotypic variation in PROP taste sensitivity are alleles of the TAS2R38 gene, which encodes a chemosensory receptor sensitive to thiourea compounds including PROP and phenylthiocarbamide. Members of the TAS2R family are expressed in the gustatory system, where they function as bitter taste receptors, and throughout the gut, where their physiological roles in prandial, gut-derived hormone release are beginning to be elucidated. To better understand the relationship between TAS2R function and ingestive behaviors, we asked if TAS2R38 variants are associated with one or more of three eating behaviors: restraint, disinhibition, and hunger. We genotyped a single nucleotide polymorphism (SNP) located within the TAS2R38 gene, rs1726866 (T785C, Val262Ala) in 729 nondiabetic individuals (381 females, 348 males) within the Amish Family Diabetes Study. Eating behaviors were assessed using the Three-Factor Eating Questionnaire. An association analysis between rs1726866 and these three traits revealed a significant association of the PROP-insensitive "T" allele with increased disinhibition (p=0.03). Because eating behaviors differ substantially between males and females, we subsequently performed sex-stratified analyses, which revealed a strong association in females (p=0.0002) but not in males. Analyses with other SNPs in close proximity to rs1726866 suggest that this locus is principally responsible for the association. Therefore, our results indicate that a polymorphism in TAS2R38 is associated with differences in ingestive behavior.
Project description:BACKGROUND: Genetic variants within the bitter taste receptor gene TAS2R38 are associated with sensitivity to bitter taste and are related to eating behavior in the Amish population. Sensitivity to bitter taste is further related to anthropometric traits in an genetically isolated Italian population. We tested whether the TAS2R38 variants (rs713598; rs1726866 and rs10246939) may be related to eating behavior, anthropometric parameters, metabolic traits and consumer goods intake in the German Sorbs. MATERIALS AND METHODS: The three SNPs were genotyped in a total cohort of 1007 individuals (male/female: 405/602). The German version of the three-factor eating questionnaire was completed by 548 individuals. Genetic association analyses for smoking behavior, alcohol and coffee intake, eating behavior factors (restraint, disinhibition and hunger) and other metabolic traits were analyzed. Further, by combining the three SNPs we applied comparative haplotype analyses categorizing PAV (proline-alanine-valine) carriers (tasters) vs. homozygous AVI (alanin-valine-isoleucine) carriers (non-tasters). RESULTS: Significant associations of genetic variants within TAS2R38 were identified with percentage of body fat, which were driven by associations in women. In men, we observed significant associations with 30 min plasma glucose, and area under the curve for plasma glucose (0-120 min) (all adjusted P?0.05). Further, we found that carriers of at least one PAV allele show significantly lower cigarette smoking per day (P?=?0.002) as well as, albeit non-significant, lower alcohol intake. We did not confirm previously reported associations between genetic variants of TAS2R38 and eating behavior. CONCLUSION: Our data suggest that genetic variation in TAS2R38 is related to individual body composition measures and may further influence consumer goods intake in the Sorbs possibly via individual sensitivity to bitter taste.
Project description:Bitterness perception in mammals is mostly directed at natural toxins that induce innate avoidance behaviours. Bitter taste is mediated by the G protein-coupled receptor TAS2R, which is located in taste cell membranes. One of the best-studied bitter taste receptors is TAS2R38, which recognizes phenylthiocarbamide (PTC). Here we investigate the sensitivities of TAS2R38 receptors to PTC in four species of leaf-eating monkeys (subfamily Colobinae). Compared with macaque monkeys (subfamily Cercopithecinae), colobines have lower sensitivities to PTC in behavioural and in vitro functional analyses. We identified four non-synonymous mutations in colobine TAS2R38 that are responsible for the decreased sensitivity of the TAS2R38 receptor to PTC observed in colobines compared with macaques. These results suggest that tolerance to bitterness in colobines evolved from an ancestor that was sensitive to bitterness as an adaptation to eating leaves.
Project description:The objective of this work was to develop a rapid screening method to identify the three single nucleotide polymorphisms (SNPs) in the TAS2R38 gene, with the aim of providing a significant contribution to studies designed to assess sensitivity to the bitter taste of 6-n-propylthiouracil (PROP). Specifically, the objective of this study was to characterize the TAS2R38 gene haplotypes in a group of 60 subjects with variable sensitivity to PROP and preliminarily genotyped for the rs2274333 allele (A/G) of carbonic anhydrase isoform VI gene (CA6). The molecular characterization of the TAS2R38 gene was conducted using the PCR-restriction fragment length polymorphism technique after creating artificial restriction sites upstream or downstream of the SNPs, as none of the three polymorphisms contributes to the formation of a restriction site for a specific endonuclease. The results indicate that the method described in this paper could be a valid and simple experimental strategy to identify genetic differences related to taste sensitivity to bitter taste, and could be applied as a nutrigenetics test in studies aimed at understanding people's eating behaviors.
Project description:Genetic variants in bitter-taste receptor genes have been hypothesized to negatively impact health outcomes and/or influence dietary intake and, consequently, could increase the risk of colorectal neoplasia. Using a case-control study of 914 colorectal adenoma cases/1188 controls, we explored associations among colorectal adenoma risk, dietary intake, and genetic variation in 3 bitter-taste receptor genes: TAS2R38 (rs713598, rs1726866, rs10246939), TAS2R16 (rs846672), and TAS2R50 (rs1376251). Analysis of covariance was conducted to detect trends in dietary intake across TAS2R genotypes/haplotypes. Odds ratios and 95% confidence intervals were estimated by logistic regression to test gene-adenoma risk associations. No significant associations were observed between the TAS2R38 PAV/PAV diplotype or the TAS2R16 (rs846672) polymorphism with the selected diet variables. We observed weak inverse associations between the TAS2R50 (rs1376251) C allele and dietary fiber and vegetable intake (Ps < 0.015). Odds ratios for adenoma risk were not significantly different from the null. Our findings do not support a link between these TAS2R genotypes/haplotypes and dietary intake that could impact colorectal adenoma risk. However, given the paucity of data, we cannot dismiss the possibility that these genes may influence colorectal adenoma risk in other ways, such as through impaired gastrointestinal function, particularly in subgroups of the population.
Project description:Domestic cats (felis catus) have a reputation for being rather unpredictable in their dietary choices. While their appetite for protein or savory flavors is consistent with their nutritional needs, their preference among protein-sufficient dietary options may relate to differences in the response to other flavor characteristics. Studies of domestic cat taste perception are limited, in part, due to the lack of receptor sequence information. Several studies have described the phylogenetic relationship of specific cat taste receptor sequences as compared with other carnivores. For example, domestic cats are obligate carnivores and their receptor Tas1r2, associated with the human perception of sweet, is present only as a pseudogene. Similarly, the cat perception of bitter may differ from that of other mammals due to variations in their repertoire of bitter receptor (Tas2r) genes. This report includes the first functional characterization of domestic cat taste receptors.We functionally expressed two uncharacterized domestic sequences Tas2r38 and Tas2r43 and deorphanized the receptors using a cellular functional assay. Statistical significance was determined using an unpaired, two-tailed t-test. The cat sequence for Tas2r38 contains 3 major amino acid residues known to confer the taster phenotype (PAI), which is associated with sensitivity to the bitter compounds PROP and PTC. However, in contrast to human TAS2R38, cat Tas2r38 is activated by PTC but not by PROP. Furthermore, like its human counterpart, cat Tas2r43 is activated by aloin and denatonium, but differs from the human TAS2R43 by insensitivity to saccharin. The responses of both cat receptors to the bitter ligands were concentration-dependent and were inhibited by the human bitter blocker probenecid.These data demonstrate that the response profiles of the cat bitter receptors Tas2r38 and Tas2r43 are distinct from those of their orthologous human receptors. Results with cat Tas2r38 also demonstrate that additional residues beyond those classically associated with PROP sensitivity in humans influence the sensitivity to PROP and PTC. Functional studies of the human bitter receptor family are being applied to the development of food and medicinal products with more appealing flavor profiles. Our work lays the foundation for similar work applied to felines.
Project description:Thiourea tasting can be predictive of individual differences in bitter taste responses, general food preferences and eating behavior, and could be correlated with saliva chemical composition. We investigated the possible relationship between PROP bitter taste responsiveness and the salivary proteome in subjects genotyped for TAS2R38 and gustin gene polymorphisms. Taste perception intensity evoked by PROP and NaCl solutions was measured in sixty-three volunteers (21 males, 42 females, age 25±3 y) to establish their PROP taster status, and 24 PROP super-tasters and 21 nontasters were selected to participate in the study. TAS2R38 and gustin gene molecular analysis were performed using PCR techniques. Qualitative and quantitative determination of salivary proteins was performed by HPLC-ESI-MS before and after PROP taste stimulation. PROP super-tastings was strongly associated with the 'taster' variant (PAV haplotype) of TAS2R38 and the A allele of rs2274333 polymorphism in the gustin gene and nontasting was associated with the minor alleles at both loci. ANOVA revealed that basal levels of II-2 and Ps-1 proteins, belonging to the basic proline-rich protein (bPRPs) family, were significantly higher in PROP super-taster than in nontaster un-stimulated saliva, and that PROP stimulation elicited a rapid increase in the levels of these same proteins only in PROP super-taster saliva. These data show for the first time that responsiveness to PROP is associated with salivary levels of II-2 peptide and Ps-1 protein, which are products of the PRB1 gene. These findings suggest that PRB1, in addition to TAS2R38 and gustin, could contribute to individual differences in thiourea sensitivity, and the expression of the PROP phenotype as a complex genetic trait.
Project description:Practical and reliable methods for the objective measure of taste function are critically important for studying eating behavior and taste function impairment. Here, we present direct measures of human gustatory response to a prototypical bitter compound, 6-n-propyltiouracil (PROP), obtained by electrophysiological recordings from the tongue of subjects who were classified for taster status and genotyped for the specific receptor gene (TAS2R38), and in which taste papilla density was determined. PROP stimulation evoked negative slow potentials that represent the summated depolarization of taste cells. Depolarization amplitude and rate were correlated with papilla density and perceived bitterness, and associated with taster status and TAS2R38. Our study provides a robust and generalizable research tool for the quantitative measure of peripheral taste function, which can greatly help to resolve controversial outcomes on the PROP phenotype role in taste perception and food preferences, and be potentially useful for evaluating nutritional status and health.
Project description:The aims of this review were to understand the roles of bitter taste genes in humans. Some of the peoples have the capacity to taste some chemical substance such as phenylthiocarbamide (PTC) while others cant not based on the dietary hazards and food preferences. There are two alleles responsible to express these phenotypes which are homozygous recessive. In human TAS2R38 genes located on the chromosome number 7 and consist of different nucleotide polymorphism that related to detection of the phenotype of different chemical compounds such as 6-n-propylthiouracil (PROP) and phenylthiocarbamide bitterness and this Gene is the member of the TAS2R genes which are eleven pseudogenes and twenty that has roles in many biological processes. There are many factors that affect the bitter taste such as food, age, sex, and different diseases. The mechanism of food bitter taste and genotype of TAS2R38 until know not well understood due to that the proof of relation between bitter taste sensitivity and food is harmful. there are many different diseases can impact the influence of taste such as neoplasm and lifestyle such as consumption of alcohol along with the use of medication, head trauma, upper tract infections. On the other hand, A relation between TAS2R38 genotype and meal preferences has been observed among children, however, no associations have been mentioned among older adults. Some previous research proved some vital points that show an association between type 1 of diabetes and phenylthiocarbamide (PTC) but other studies cannot demonstrate that. However, of other disease such as obesity is controversial but other studies reported to the relationship between them.
Project description:Alleles of the receptor gene TAS2R38 are responsible in part for the variation in bitter taste perception of 6-n-propylthiouracil (PROP) and structurally similar compounds (eg, glucosinolates in cruciferous vegetables). At low concentrations, people with the PAV ("taster" amino acid sequence) form of TAS2R38 perceive these bitter compounds, whereas most with the AVI ("nontaster" amino acid sequence) form do not; heterozygotes (PAV/AVI) show the widest range of bitter perception.The objectives were to examine individual differences in expression of PAV-TAS2R38 messenger RNA (mRNA) among heterozygotes, to test the hypotheses that the abundance of allele-specific gene expression accounts for the variation in human bitter taste perception, and to relate to dietary intake of bitter-tasting beverages and foods.Heterozygous individuals (n = 22) provided psychophysical evaluation of the bitterness of PROP, glucosinolate-containing broccoli juice, non-glucosinolate-containing carrot juice, and several bitter non-TAS2R38 ligands as well as dietary recalls. Fungiform taste papillae were examined for allele-specific TAS2R38 expression by using quantitative polymerase chain reaction.PAV-TAS2R38 mRNA expression was measured in 18 of 22 heterozygous subjects. Relative expression varied widely and positively correlated with ratings of bitterness intensity of PROP (P = 0.007) and broccoli juice (P = 0.004) but not of the control solutions carrot juice (P = 0.26), NaCl (P = 0.68), caffeine (P = 0.24), or urea (P = 0.47). Expression amounts were related to self-reported recent and habitual caffeine intake (P = 0.060, P = 0.005); vegetable intake was too low to analyze.We provide evidence that PAV-TAS2R38 expression amount correlates with individual differences in bitter sensory perception and diet. The nature of this correlation calls for additional research on the molecular mechanisms associated with some individual differences in taste perception and food intake. The trial was registered at clinicaltrials.gov as NCT01399944.
Project description:The purpose of this study was to validate the use of edible taste strips for measuring taste recognition thresholds for the bitter-tasting compound 6-n-propylthiouracil (PROP).Taste recognition thresholds for PROP were obtained by two separate methods. Thresholds were also identified in subjects whose airflow through the nose was blocked. Threshold values were then compared to genotype analysis of the TAS2R38 taste receptor, which is the major determinant for the detection of PROP.Edible taste strips were used to examine taste recognition thresholds for PROP. Thresholds were determined by the method of ascending limits and by the method of reversals. Single nucleotide polymorphism analysis of the TAS2R38 gene was used to identify PROP taster status.Taste recognition thresholds for PROP formed two distributions. Thresholds for one group varied from 4 to 219 nmol and represented PROP tasters. The second group could not detect the bitter taste of PROP at ?800 nmol and represented PROP nontasters. The method of ascending limits and the method of reversals yielded similar threshold results. The expression of a PAV allele permitted detection of PROP, but AVI homozygotes could not detect the bitter taste of PROP.Edible taste strips were successfully used to detect PROP thresholds at values equal to or lower than those obtained in previous studies using PROP solutions or PROP-impregnated filter papers. This study provides validity evidence for the use of edible taste strips for identifying PROP in the human population.