Bitter Taste Receptor TAS2R38 Research Articles

Insights into the dynamic evolution of quality and sensory attributes in red aril wine during fermentation

Red arils, derived from the yew tree (Taxus spp.), are renowned for their edible and nutritional properties. In this study, a novel red aril (RA) wine was produced and evaluated for its quality characteristics and sensory attributes. The flavor compounds in RA wine changed dynamically during fermentation, with a total of 26 differential volatiles identified. PLSR analysis indicated that ketones positively contributed to the citrus odor. Furthermore, RA wine exhibited high levels of organic acids, polyphenols, and amino acids after fermentation, influencing its bitterness and sourness profile. Molecular docking revealed that the activation of receptor OR1G1 by 6-methyl-5-hepten-2-one, a key ketone volatile, generated the citrus odor in RA wine. Furthermore, the taste profile of RA wine was inclined towards bitterness and sourness. Molecular docking analysis also demonstrated interactions between the key differential taste compounds with bitter-taste receptor TAS2R14 and sour-taste receptor OTOP1. Moreover, an intricate metabolic profile of RA wine was revealed through an overall metabolic map, providing insights into the underlying formation mechanisms contributing to RA wine quality.

The Influence of Taste Genes on Body Fat and Alcohol Consumption.

Dietary intake and alcohol consumption might be influenced by genetic variations in taste receptor genes. The objectives of this study were to examine the relationship between polymorphisms in the bitter taste receptor genes TAS2R13 (rs1015443) and TAS2R38 (rs1726866, rs10246939, and rs713598) as well as alcohol consumption and body fat percentage in college students. Four hundred and two students with a mean age of 20.2 years participated in this study. An NIH Diet History Questionnaire (DHQ II) was used to collect data on their dietary intake, while an AUDIT survey was used to determine their level of alcohol consumption. Bitter taste receptor gene polymorphisms were assessed by TaqMan allelic discrimination assays. Despite significant associations between TAS2R13 (rs1015443) and certain aspects of alcohol consumption, including the frequency of alcohol intake, no significant associations were found between TAS2R13 (rs1015443) and alcohol consumption after accounting for confounding variables in the regression model. Neither association was found regarding percent of body fat. In contrast, ethnicity and gender significantly influenced percent of body fat (p < 0.001), while no significant association was observed between TAS2R13 (rs1015443) and percent of body fat. Likewise, TAS2R38 (rs1726866, rs10246939, and rs713598) demonstrated no significant association with alcohol consumption and percent of body fat. These results were controlled for confounding factors, such as ethnicity and gender. Body fat percentage and alcohol consumption may be influenced by ethnicity, gender, and age rather than SNPs of TAS2R13 and TAS2R38 genes. Assessing taste genes' interactions with diet and body composition might be useful in identifying human disease risk.

TAS2R38 Bitter Taste Receptor Polymorphisms in Patients with Chronic Rhinosinusitis with Nasal Polyps Preliminary Data in Polish Population.

Chronic rhinosinusitis (CRS) affects 5-12% of the general population, and the most challenging patients are those with nasal polyposis (CRSwNP). Its complexity, unpredictability, and difficulties in selecting a treatment plan individually for each patient prompted scientists to look for possible genetic causes of this disease. It was proven that single nucleotide polymorphisms (SNPs) in the TAS2R38 gene may affect the mobility and the activity of the ciliated epithelium of the upper respiratory tract what can contribute to individual differences in susceptibility to CRS. There are two common haplotypes: a "protective" type (PAV), and a "non-protective" type (AVI). CRS patients who are homozygous PAV/PAV are considered as less susceptible to the severe course of the disease, whereas patients with AVI/AVI haplotype are more vulnerable. The aim of this study was to examine TAS2R38 gene polymorphisms among CRSwNP patients and control group (N = 544) with the evaluation of the association between the distribution of studied polymorphic variants and the incidence as well as severity of CRSwNP in the study group. Whole blood samples from CRSwNP patients (N = 106) and the control group (N = 438) were analyzed for alleles of the TAS2R38 gene using real-time PCR single nucleotide polymorphism genotyping assays for rs713598, rs1726866, and rs10246939. PAV (SG: 41%; CG: 49%) and AVI (SG: 59%; CG: 51%) haplotypes were the only ones detected in the study. The AVI haplotypes were 1.5 times more frequent in the study group than in the control group (p = 0.0204; OR = 1.43). AVI/AVI individuals tended to have more severe symptoms in the VAS scale, less QoL in the SNOT-22 test, and a bigger nasal obstruction upon endoscopic examination. Patients with PAV/PAV were twice more likely to have minor changes in preoperative CT scans (p = 0.0158; OR = 2.1; Fi = 0.24). Our study confirmed that the PAV/PAV diplotype might have some protective properties and carrying the AVI haplotype might predispose to the development of CRSwNP.

Association between Genetic Variation in the TAS2R38 Bitter Taste Receptor and Propylthiouracil Bitter Taste Thresholds among Adults Living in Japan Using the Modified 2AFC Procedure with the Quest Method.

Individual taste sensitivity influences food preferences, nutritional control, and health, and differs greatly between individuals. The purpose of this study was to establish a method of measuring and quantifying an individual's taste sensitivity and to evaluate the relationship between taste variation and genetic polymorphisms in humans using agonist specificities of the bitter taste receptor gene, TAS2R38, with the bitter compound 6-n-propylthiouracil (PROP). We precisely detected the threshold of PROP bitter perception by conducting the modified two-alternative forced-choice (2AFC) procedure with the Bayesian staircase procedure of the QUEST method and examined genetic variation in TAS2R38 in a Japanese population. There were significant differences in PROP threshold between the three TAS2R38 genotype pairs for 79 subjects: PAV/PAV vs AVI/AVI, p < 0.001; PAV/AVI vs AVI/AVI, p < 0.001; and PAV/PAV vs PAV/AVI, p < 0.01. Our results quantified individual bitter perception as QUEST threshold values: the PROP bitter perception of individuals with the PAV/PAV or PAV/AVI genotypes was tens to fifty times more sensitive than that of an individual with the AVI/AVI genotype. Our analyses provide a basic model for the accurate estimation of taste thresholds using the modified 2AFC with the QUEST approach.

Discovery of 2-Aminopyrimidines as Potent Agonists for the Bitter Taste Receptor TAS2R14.

The bitter taste receptor TAS2R14 is a G protein-coupled receptor that is found on the tongue as well as in the human airway smooth muscle and other extraoral tissues. Because its activation causes bronchodilatation, TAS2R14 is a potential target for the treatment of asthma or chronic obstructive pulmonary disease. Structural variations of flufenamic acid, a nonsteroidal anti-inflammatory drug, led us to 2-aminopyridines showing considerable efficacy and potency in an IP1accumulation assay. In combination with an exchange of the carboxylic moiety by a tetrazole unit, a set of promising new TAS2R14 agonists was developed. The most potent ligand 28.1 (EC50 = 72 nM) revealed a six-fold higher potency than flufenamic acid and a maximum efficacy of 129%. Besides its unprecedented TAS2R14 activation, 28.1 revealed marked selectivity over a panel of 24 non-bitter taste human G protein-coupled receptors.

Automated identification of the genetic variants of TAS2R38 bitter taste receptor with supervised learning

Several studies were focused on the genetic ability to taste the bitter compound 6-n-propylthiouracil (PROP) to assess the inter-individual taste variability in humans, and its effect on food predilections, nutrition, and health. PROP taste sensitivity and that of other chemical molecules throughout the body are mediated by the bitter receptor TAS2R38, and their variability is significantly associated with TAS2R38 genetic variants. We recently automatically identified PROP phenotypes with high precision using Machine Learning (mL). Here we have used Supervised Learning (SL) algorithms to automatically identify TAS2R38 genotypes by using the biological features of eighty-four participants. The catBoost algorithm was the best-suited model for the automatic discrimination of the genotypes. It allowed us to automatically predict the identification of genotypes and precisely define the effectiveness and impact of each feature. The ratings of perceived intensity for PROP solutions (0.32 and 0.032 mM) and medium taster (MT) category were the most important features in training the model and understanding the difference between genotypes. Our findings suggest that SL may represent a trustworthy and objective tool for identifying TAS2R38 variants which, reducing the costs and times of molecular analysis, can find wide application in taste physiology and medicine studies.

Genetic variations in bitter and sweet taste receptors in Taiwanese patients with chronic rhinosinusitis.

Genetic variations of bitter and sweet taste receptors have been related to the pathophysiology of chronic rhinosinusitis (CRS). In this study, we attempted to explore the genetic variations of bitter and sweet taste receptors in Taiwanese CRS patients. Five hundred and sixty-six CRS patients and 5,660 control subjects were selected from participants in the Taiwan Precision Medicine Initiative. Amongst the 566 CRS patients, 186 were with nasal polyps (CRSwNP), while the other 380 were without (CRSsNP). Surgical specimens obtained from 292 CRS patients revealed that 177 were eosinophilic CRS, with the other 115 being non-eosinophilic CRS. There were 591,048 single nucleotide polymorphisms (SNPs) for analysis in all the eligible subjects, including 2 bitter taste receptor SNPs (rs713598, rs10246939) and 1 sweet taste receptor SNP (rs35874116). The minor allele frequencies (MAFs) of rs713598, rs10246939 and rs35874116 were 0.298, 0.297 and 0.078 for CRS patients and 0.306, 0.306 and 0.087 for the control subjects, were 0.301. 0.301 and 0.067 in CRSwNP patients, and 0.295, 0.295 and 0.084 in CRSsNP patients, and were 0.302, 0.302 and 0.085 in the eosinophilic CRS patients, and 0.283,0.287 and 0.087 in the non-eosinophilic CRS patients. The MAFs of rs713598, rs10246939 and rs35874116 were not significantly different between CRS patients and control subjects, between CRSwNP and CRSsNP patients, and between eosinophilic CRS and non-eosinophilic CRS patients. We did not find an association between three variants of the bitter taste receptor TAS2R38 and the sweet taste receptor TAS1R2 and Taiwanese CRS patients. This article is protected by copyright. All rights reserved.

TAS2R38 Bitter Taste Receptor Expression in Chronic Rhinosinusitis with Nasal Polyps: New Data on Polypoid Tissue.

Studies have shown differences in TAS2R38 receptor expression in patients with chronic rhinosinusitis (CRS) compared to healthy controls. Known agonists of TAS2R38 stimulate epithelial cells, leading to robust intracellular nitric oxide (NO) production, which damages bacterial membranes, enzymes, and DNA, but also increases ciliary beat frequency. In this study we examined, using qRT-PCR, the expression of TAS2R38 receptor in nasal polyps (NP) of patients with CRS (N = 107) and in inferior turbinate mucosa (ITM) of patients with CRS and controls (N = 39), and confronted it with clinical features and the severity of the disease. The expression was shown in 43 (50.00%) samples of ITM in the study group (N = 107), in 28 (71.79%) in the control group (N = 39) (p = 0.037), and in 43 (46.24%) of NP. There were no differences in levels of the expression in all analyzed tissues. Patients who rated their symptoms at 0–3 showed higher TAS2R38 expression in ITM in comparison to the patients with 8–10 points on the VAS scale (p = 0.020). A noticeable, however not significant, correlation between the TAS2R38 expression in ITM and the Lund–Mackay CT score was shown (p = 0.068; R = −0.28). Patients with coexisting asthma had significantly higher receptor expression in the NP (p = 0.012). Our study is the first to confirm the presence of the TAS2R38 receptor in NP. Expression of the TAS2R38 receptor is reduced in the sinonasal mucosa in patients with more advanced CRS with NP.

The Bitter Taste Receptor TAS2R14 as a Drug Target

G protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants. Besides human senses like vision and olfaction, taste perception is mostly mediated by GPCRs. Hence, the bitter taste receptor family TAS2R comprises 25 distinct receptors and plays a key role in food acceptance and drug compliance. The TAS2R14 subtype is the most broadly tuned bitter taste receptor, recognizing a range of chemically highly diverse agonists. Besides other tissues, it is expressed in human airway smooth muscle and may represent a novel drug target for airway diseases. Several natural products as well as marketed drugs including flufenamic acid have been identified to activate TAS2R14, but higher potency ligands are needed to investigate the ligand-controlled physiological function and to facilitate the targeted modulate for potential future clinical applications. A combination of structure-based molecular modeling with chemical synthesis and in vitro profiling recently resulted in new flufenamic acid agonists with improved TAS2R14 potency and provided a validated and refined structural model of ligand–TAS2R14 interactions, which can be applied for future drug design projects.

Distribution of TAS2R38 bitter taste receptor phenotype and haplotypes among COVID-19 patients.

Bitter taste receptor TAS2R38 is expressed in the respiratory tract and can respond to quorum-sensing molecules produced by pathogens, stimulating the release of nitric oxide, with biocidal activity. TAS2R38 presents two main high-frequency haplotypes: the “taster” PAV and the “non-taster” AVI. Individuals carrying the AVI allele could be at greater risk of infections, including SARS-CoV-2. The aim of this study was to assess the frequency of PAV and AVI alleles in COVID-19 patients with severe or non-severe symptoms compared to healthy subjects to further corroborate, or not, the hypothesis that the PAV allele may act as a protecting factor towards SARS-CoV-2 infection while the AVI one may represent a risk factor. After careful selection, 54 individuals were included in the study and underwent genetic analysis and PROP phenotype assessment. Our investigation could not point out at a significant relationship between single nucleotide polymorphisms responsible for PROP bitterness and presence/severity of SARS-CoV-2 infection, as previous studies suggested. Our results uncouple the direct genetic contribution of rs10246939, rs1726866 and rs713598 on COVID-19, calling for caution when proposing a treatment based on TAS2R38 phenotypes.

Chronic Rhinosinusitis: T2r38 Genotyping and Nasal Cytology in Primary Ciliary Dyskinesia.

Chronic rhinosinusitis (CRS) is a major hallmark of primary ciliary dyskinesia (PCD). We investigated the possible correlation between some severity markers of CRS and several clinical features of the disease. We further studied the bitter taste receptor TAS2R38 polymorphisms to identify the genotypes associated with more severe disease. We included 39 adult PCD patients with (CRSwNP) and without nasal polyposis (CRSsNP); a sample for nasal cytology was obtained and clinical cytological grading (CCG) was determined. The SNOT-22 and Lund-Mackay scores were recorded. A sample of DNA was extracted from peripheral blood to investigate TAS2R38 polymorphisms. CRSwNP patients had features of more severe disease: indeed, they had statistically significantly higher frequency of previous sinus surgery, higher SNOT-22, LM scores, and CCG than CRSsNP patients. Upon genotyping of TAS2R38 polymorphisms, we observed that the AVI-AVI genotype, associated to homozygous nonfunctional bitter TAS2R38 receptor, was more prevalent among CRSwNP (100%) than in CRSsNP patients (0%); furthermore, AVI-AVI subjects showed statistically significantly worse SNOT-22 and CCG scores than PAV-PAV and PAV-AVI subjects. The group of AVI-AVI patients also had more frequent respiratory exacerbations, Gram-negative infections, and Pseudomonas aeruginosa colonization than PAV-PAV and PAV-AVI patients. Our findings indicate for the first time that PCD patients with CRSwNP display a more severe disease than those with CRSsNP. Genotyping of TAS2R38 polymorphisms demonstrated that in PCD patients, the AVI-AVI genotype is strikingly more prevalent among CRSwNP than in CRSsNP, while the PAV-PAV genotype might be protective against Gram-negative infections and respiratory exacerbations. 3 Laryngoscope, 133:248-254, 2023.

TAS2R38 polymorphisms and oral diseases in Thais: a cross-sectional study

BackgroundPolymorphisms at positions 49, 262, and 296 in the TAS2R38 bitter taste receptor gene result in two common genetic haplotypes, PAV and AVI, named for the resulting amino acid substitutions. TAS2R38 genotype has been previously associated with caries risk in children. This study aimed to identify TAS2R38 polymorphisms among Thais and to explore any association between genotype and oral diseases.MethodsPatients seeking care at Khon Kaen University Dental Hospital in Thailand were recruited to participate in the study. Saliva was collected for DNA extraction and genotyping. Patients completed a questionnaire to collect demographic variables and assess oral self-care behaviors. A calibrated dentist conducted an examination that included periodontal charting and recording of decayed, missing, and filled teeth (DMFT).ResultsA total of 250 patients (19–75 years) were enrolled in the study (116 males). Two haplotypes, PAV (67.2%) and AVI (32.8%) were found, resulting in 3 diplotypes; PAV/PAV (46.0%), PAV/AVI (42.4%) and AVI/AVI (11.6%). DMFT and periodontal status of 238 participants were recorded. The three diplotype groups were similar in age, sex, socio-economic indicators, oral self-care, and number of teeth. The odds of having periodontal disease, defined as at least one site with probing depth ≥ 5 mm, were lower in AVI/AVI and PAV/AVI compared with PAV/PAV. PAV/AVI tended to have less DMFT, while AVI/AVI tended to have more DMFT compared with PAV/PAV, however these trends did not reach statistical significance.ConclusionsThe frequency distribution of TAS2R38 genotypes was similar to that reported for other Asian populations. AVI/AVI genotype was associated with decreased prevalence of periodontal disease among Thai dental patients, whereas there was no significant association between TAS2R38 genotype and prevalence of tooth decay in this patient population.

Identification of Oncorhynchus mykiss nebulin-derived peptides as bitter taste receptor TAS2R14 blockers by in silico screening and molecular docking

Human bitter taste receptor TAS2R14 (T2R14) can widely perceive bitterness, which has always been an issue for people to overcome. This study was aimed at identifying bioactive peptides obtained from Oncorhynchus mykiss nebulin hydrolysates as bitter taste receptor blockers by physicochemical property prediction, molecular docking, and in vitro determination of bitterness intensity using electronic tongue. Exploration of the interaction mechanism of these peptides with T2R14 by molecular docking models indicated that peptides ADM and ADW had high affinities for T2R14 to block the binding of bitter substances into the receptor. Addition of ADM and ADW to quinine caused reduction in bitterness intensity, with IC50 values of 420.32 ± 6.26 μM and 403.29 ± 4.10 μM, respectively. Hydrogen bond interaction and hydrophobic interaction were responsible for manifesting the high affinities of these peptides for the receptor. Residues Thr86, Asp168, and Phe247 may be the key amino acids within the binding site.

Taste perception and expression in stomach of bitter taste receptor tas2r38 in obese and lean subjects

Differences in taste perception have been related to eating behavior, nutritional status, and diseases. Recently, taste receptors have been identified in several extra-oral tissues, such as the gastrointestinal tract, where they seem to influence processes like digestion, sense of satiety as well as energy balance and intraluminal changes occurring in obesity.Our study aims to analyze differences in taste perception among 42 obese patients (OB) and 41 normal-weight subjects (LEAN). Polymorphisms in the gene codifying for the bitter taste receptor TAS2R38 and its expression on the surface of the gastric mucosa were tested and compared among OB and LEAN.Taste intensity of PROP (6-n-propylthiouracil), quinine, sucrose, citric acid and NaCl were measured on a labeled magnitude scale. DNA from peripheral whole blood was extracted and three polymorphisms in the TAS2R38 gene (rs713598, rs1726866, rs10246939) analyzed. Gastric biopsies were collected during bariatric surgery in OB and during endoscopy in LEAN. RNA was extracted and TAS2R38 gene expression assessed by RT-Real-Time qPCR. Anamnestic and anthropometric data were recorded in all participants during baseline visits.Logistic regression analysis showed that OB perceives sweet (sucrose) and bitter (PROP or 6-n-propylthiouracil) taste more intensely than LEAN (p-value = 0.02 and p-value = 0.005, respectively). While polymorphisms in TAS2R38 gene did not differ among OB and LEAN, we observed a significant increase of TAS2R38 mRNA levels in the stomach of OB compared to LEAN (p = 0.01).Our results provide new evidence of a link between obesity and altered taste perception as well as TAS2R38 expression in the stomach.

Expression of TAS2R14 in the intestinal endocrine cells of non-human primates.

Recent studies have demonstrated that genes related to bitter taste receptors (TAS2Rs) on various chromosomes are expressed in extra-oral organs of various animals. The bitter taste receptor TAS2R14 is conserved among primate species and shows broad ligand sensitivity. Mice have a number of orthologues to primate TAS2R14 located in tandem on chromosome 16; however, their expression patterns are not unique. We characterized the expression of TAS2R14 in various cell types in the intestines of the rhesus macaque and evaluated its role in hormone production in the gut. TAS2R14 expression was examined in the intestines of rhesus macaques, a common non-human primate model, by RT-qPCR and immunohistochemical staining. Mean expression levels of TAS2R14 in the duodenum, ileum, and colon were similar to each other and were lower than those in circumvallate papillae. An immunohistochemical analysis revealed TAS2R14 immunoreactivity in enteroendocrine cells positive for cholecystokinin, serotonin, and the G protein GNAT3. These results suggest that primate TAS2R14 is broadly expressed in the intestine, mainly in enteroendocrine cells, and promotes gut hormone secretion in response to bitter stimuli.

Functionally expressed bitter taste receptor TAS2R14 in human epidermal keratinocytes serves as a chemosensory receptor.

Traditionally, it is theorized that skin sensation is initiated when cutaneous sensory afferents and Merkel cells receive sensory stimuli, while epidermal keratinocytes were deemed to have no role. However, mounting evidence has shown that keratinocytes can initiate skin sensation by receiving sensory stimuli and transmitting sensory information to sensory afferents. Knowledge regarding the mechanisms by which keratinocytes receive exogenous stimuli is limited, with TRP channels and olfactory receptors having been proposed to serve as receptors for exogenous stimuli in keratinocytes. Recently, expression analyses have demonstrated the expression of multiple TAS2R genes in human skin. TAS2Rs are chemosensory GPCRs employed by taste cells to detect bitter-tasting substances. However, only subtypes TAS2R1 and TAS2R38 have been characterized in epidermal keratinocytes. We present evidence suggesting that subtype TAS2R14 is functionally expressed in epidermal keratinocytes. TAS2R14 transcripts and protein were detected in primary and N/TERT-1 keratinocytes. Additionally, keratinocytes responded to α-thujone, a TAS2R14 ligand, with an increase in intracellular free Ca2+ concentration. The tastant-evoked Ca2+ signals were found to be mediated by wild-type TAS2R14 and heterotrimeric G proteins. We conclude that TAS2R14 serves as a chemosensory receptor in epidermal keratinocytes and hypothesize that it enables the cells to recognize potentially harmful chemical substances.

Genetic variants of TAS2R38 bitter taste receptor associate with distinct gut microbiota traits in Parkinson's disease: A pilot study

The non-tasting form of the bitter taste receptor, TAS2R38, has been shown as a genetic risk factor associated with the development of Parkinson's disease (PD). Specific taste receptors that are expressed in the lower gastrointestinal tract may respond to alteration in gut microbiota composition, detecting bacterial molecules, and regulate immune responses. Given the importance of brain-gut-microbiota axis and gene-environment interactions in PD, we investigate the associations between the genetic variants of TAS2R38 and gut microbiota composition in 39 PD patients. The results confirm that the majority of PD patients have reduced sensitivity to 6-n-propylthiouracil (PROP) and are carriers of at least one non-functional TAS2R38 AVI haplotype. Moreover, we found this correlation to be associated with a reduction in bacteria alpha-diversity with a predominant reduction of Clostridium genus. We hypothesised that the high frequency of the non-taster form of TAS2R38 associated with a diminuition of Clostridium bacteria in PD might determine a reduction in the activation of protective signalling-molecules useful in preserving gut homeostasis. This pilot study, by identifying a decrease in specific bacteria associated with a reduced sensitivity to PROP, adds essential information that opens new avenues of research into the association of PD microbiota composition and sensory modification.

The expression of bitter taste receptor TAS2R38 in patients with chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a frequent disease with high social impact and multifactorial pathogenesis. Recently, the bitter taste receptor TAS2R38 has been described to play a role in upper airway innate mucosal defense. The aim was to determine the localization and expression of the TAS2R38 in the selected cell lines and tissue collected from patient suffered from CRS as well as to correlate the results with clinical data. Moreover, the purpose was the estimation of the TAS2R38 distribution changes during acute and CRS. Forty-two patients undergoing nasal surgery were enrolled in the study. The TAS2R38 expression was assessed in the collected tissues using immunohistochemistry and immunocytochemistry methods. The western blot analysis was performed on human cell lines HeLa, MCF7, MDA-MB-231 to assess the location of the TAS2R38 protein. Moreover, the HeLa cell line was used as a model of acute inflammation induces by lipopolysaccharide. Immunohistochemistry analysis displayed a statistically significant difference of TAS2R38 level in the patients with CRS compared to healthy control and was different in CRS with and without nasal polyps. The results showed the abundance of TAS2R38 receptor in the cell nucleus in patients with CRS and cell lines. The variance in TAS2R38 receptor expression in two CRS types suggests their different pathogenesis. The first time in literature, we confirmed the presence of plasma membrane TAS2R38 receptor in the cell nuclei in CRS as well as in cell lines, what strongly suggests the different than membrane TAS2R38 function.

Bitter Taste Sensitivity Is Determined by TAS2R38 Haplotype, Associated with Saturated Fat Intake and Is Lower in Overweight and Obese Compared to Normal Weight UK adults

Abstract Objectives Taste perception (sensitivity) may be determined by genetic variations in taste receptors and it affects food intake. Lower fat taste sensitivity is associated with higher dietary fat intake and body mass index (BMI). Recently, associations between bitter and fat taste sensitivity have been reported whereby bitter taste perception may be involved in textural perception of dietary fat. However, it is not clear if lower sensitivity to bitter taste would lead to an actual higher fat intake. Our objectives were to explore the associations between haplotypes in the bitter taste receptor TAS2R38, bitter taste sensitivity and fat intake and if bitter taste sensitivity is lower in individuals with higher BMI. Methods Ethical approval was obtained from the St Mary's and Oxford Brookes University Ethics Committee. Eighty-eight healthy Caucasian participants (44% male and 56% female; mean BMI 24.9 ± 4.8 kg/m2 and mean age 35 ± 14 years) completed this cross-sectional study. Height and weight were measured and genotyping performed for rs713598, rs1726866, rs10246939 genetic variants in the TAS2R38. Haplotypes were determined with Haploview software. Participants rated the intensity of a phenylthiocarbamide (PTC) impregnated strip on the general Labelled Magnitude Scale (gLMS) to determine bitter taste sensitivity and were classified as bitter tasters and non-tasters. Dietary fat intake was calculated from the EPIC-Norfolk Food Frequency Questionnaire and expressed as % total energy intake. Results TAS2R38 haplotypes were associated with bitter taster status (P &amp;lt; 0.005). PTC ratings of intensity were negatively correlated with % saturated fat (SFA) intake (rs = −0.256, P = 0.016). %SFA and %total fat (rs = 0.656, P &amp;lt; 0.005) and %total fat and energy intake (kcal) (rs = 0.225, P = 0.035) were positively correlated. Normal weight participants rated PTC strips as more intense compared to overweight and obese participants (mean rank 53 vs. 41, P = 0.033). Conclusions Bitter taste perception is determined by genetics and lower sensitivity to this taste is associated with higher intake of SFA. Lower bitter taste sensitivity in overweight/obese participants suggests that impaired bitter taste may be associated with an overall unhealthier and more energy dense dietary pattern. Funding Sources St Mary's and Oxford Brookes University.

Assessment of the effect of inflammatory changes and allergic reaction on TAS2R38 receptor expression in patients with chronic sinusitis (CRS).

&lt;b&gt;Background:&lt;/b&gt; Chronic rhinosinusitis (CRS) is one of the most common health complaints affecting 15% of the world's population. Recent reports confirm the participation of sensory organs in the defense process against pathogenic microorganisms. The bitter taste receptor TAS2R38 is described to play a role in the upper airway defense system. &lt;br&gt;&lt;b&gt;Purpose:&lt;/b&gt; The purpose of this study was to assess the function of the bitter taste receptor in correlation with the severity of CRS, sensory organ disorders and allergic reaction. &lt;br&gt;&lt;b&gt;Material and method: &lt;/b&gt;The study contained 100 patients undergoing nasal surgery, divided into two groups: CRS with and without nasal polyps. The control group consisted of patients undergoing septoplasty after excluding rhinosinusitis. Sinus mucosa samples obtained during surgery were used to assess TAS2R38 expression using immunohistochemistry. The IgE level was indicated from blood samples collected from patients. The Sniffin' Sticks Test was performed. &lt;br&gt;&lt;b&gt;Results:&lt;/b&gt; CRS patients had higher expression of TAS2R38 receptor compared to controls (p = 0.0175). A statistically significantly higher TAS2R38 H-score in nasal mucosa was found among patients with a higher inflammation process in CT scan (p = 0.001), higher IgE level (p = 0,04) and an abnormal result of the Sniffin' Sticks Test. &lt;br&gt;&lt;b&gt;Conclusions: &lt;/b&gt;Patients with CRS had significant TAS2R38 receptor overexpression correlating with the severity of inflammatory changes in CT scans, abnormal perception of smells and higher IgE level. A cumulative impact was found between the inflammatory changes, smell disfunction and the severity of subjective symptoms of CRS (according to EPOS) and the intensity of cell staining (index H-score).