TAS2R38 Polymorphisms Research Articles

Impact of TAS2R38 polymorphisms on nasal nitric oxide and Pseudomonas infections in primary ciliary dyskinesia: relation to genotype

ObjectivePrimary ciliary dyskinesia (PCD) severity has been related to genotype and levels of nasal nitric oxide (nNO). The most common TAS2R38 haplotypes (PAV/PAV, PAV/AVI, AVI/AVI) encoding the bitter taste receptor...

A meta-analysis on polymorphic trait of taste perception mediated by TAS2R38 genotype.

The objective of this study is to review the association of TAS2R38 polymorphisms and taste phenotypes to bitter compounds (phenylthiocarbamide [PTC]/propylthiouracil [PROP]), and its association among persons who drink alcohol and individuals with smoking behavior. A literature search was carried out in PubMed, ScienceDirect, Cochrane, and Wiley online library databases using the keyword "(Bitter taste receptor genes OR TAS2R38) AND (PROP OR propylthiouracil) AND (PTC OR phenylthiocarbamide)," "(Bitter taste receptor genes OR TAS2R38) AND (alcohol)," "(Bitter taste receptor genes OR TAS2R38) AND (tobacco OR smoker)" to find articles evaluating the association of taste phenotypes and TAS2R38 polymorphisms, and its association among persons who drink alcohol and individuals with smoking behavior. The analysis show that TAS2R38 taster genotype (proline-alanine-valine [PAV] allele) was significantly (OR, 5.88; CI [3.87, 8.95], p < .001) associated with taster phenotype for bitter compounds (PTC/PROP), and TAS2R38 nontaster genotype (alanine-valine-isoleucine allele) was significantly (OR, 6.73; CI [4.57, 9.90], p < .001) associated with nontaster phenotype for bitter compounds. Further, TAS2R38 taster genotypes (PAV homozygotes and heterozygotes) were significantly associated with higher alcohol intake (OR, 5.15; 95% CI [2.66, 9.98]; p < .001) and among individuals with smoking behavior (OR, 1.73; 95% CI [1.24, 2.42]; p = .001). This suggests that TAS2R38 single nucleotide polymorphisms can be identified by clinically assessing taste phenotype status for bitter compounds and can be used as a potential therapeutic target in the prevention and treatment of harmful higher alcohol intake and smoking behavior. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

TAS2R38 Genotype Does Not Affect SARS-CoV-2 Infection in Primary Ciliary Dyskinesia.

Several chronic respiratory diseases could be risk factors for acquiring SARS-CoV-2 infection: among them, Primary Ciliary Dyskinesia (PCD) is a rare (about 1:10.000) inherited ciliopathy (MIM 242650) characterized by recurrent upper and lower respiratory tract infections due to a dysfunction of the respiratory cilia. In this study, we aimed to investigate whether PCD subjects are more susceptible to infection by SARS-CoV-2 and whether some polymorphisms of the TAS2R38 bitter taste receptor correlate with an increased prevalence of SARS-CoV-2 infection and severity of symptoms. Patients answered several questions about possible SARS-CoV-2 infection, experienced symptoms, and vaccinations; in the case of infection, they also filled out a SNOT-22 questionnaire and ARTIQ. Forty PCD adult patients (mean age, 36.6 ± 16.7 years; 23 females, 17 males) participated in this study, out of which 30% had tested positive for COVID-19 during the last four years; most of them reported a mildly symptomatic disease. We found no differences in age or sex, but a statistically significant difference (p = 0.03) was observed in body mass index (BMI), which was higher in the COVID-acquired group (23.2 ± 3.3 vs. 20.1 ± 4.1 kg/m2). Genotyping for TAS2R38 polymorphisms showed a prevalence of 28.6% PAV/PAV, 48.6% PAV/AVI, and 22.8% AVI/AVI individuals in our cohort. In contrast to our hypothesis, we did not observe a protective role of the PAV allele towards SARS-CoV-2 infection. Conclusions: Our findings suggest that subjects with PCD may not be at increased risk of severe outcomes from COVID-19 and the TAS2R38 bitter taste receptor genotype does not affect SARS-CoV-2 infection.

Genetic and Phenotypic Variations in Phenylthiocarbamide Bitter Taste Receptors in Iraqi Population

Bitter substances are identified by protein receptors located on surface of taste cell membranes. Mutational polymorphism of the bitter taste receptor (TAS2R38) is a significant determinant in phenylthiocarbamide (PTC) threshold perception. This research's objectives were to find TAS2R38 polymorphisms in Iraqi people and investigate any correlations between genotype and the PTC taste sensitivity. Bitterness sensitivity was determined by assessing the capacity to differentiate and the responsiveness to a representative strip of PTC. Cheek cells samples were collected for DNA extraction, PCR amplification and genotyping. PCR was performed to amplify the short region of the TAS2R38 gene containing the initial polymorphisms of interest (145G &gt; C, rs713598). Amplified samples were digested by the restriction enzyme (HaeIII) to study the genetic variations in TAS2R38 which is involved in PTC bitter sensitivity. This particular study included a total of 32 different cohorts. The phenotypic frequency of PTC strong-tasters and non-tasters was identical at 34.375% which was a greater value than the frequency of weak-tasters (31.25%). While genotypic data analysis showed that weak-tasters had a genotypic frequency of 45.16% which was higher than the genotypic frequencies of strong-taters (22.58%) and non-tasters (32.26%) respectively. In addition to this, 87.1% of the projected phenotypic and genotypic frequencies were in agreement with one another. Even though more detailed statistical analysis with a bigger group is needed. The results of this study suggest that allelic variation in the single locus TAS2R38 rs713598 works as a crucial genetic marker for bitterness sensitivity and has vital roles in the bitter tasting ability among Iraqi population.

Variations in the TAS2R38 gene among college students in Hubei

BackgroundThe bitter taste receptor gene TAS2R38 is a member of the human TAS2R gene family. Polymorphisms in TAS2R38 affect the ability to taste the bitterness of phenylthiourea (PTC) compounds, thus affecting an individual’s food preference and health status.MethodsWe investigated polymorphisms in the TAS2R38 gene and the sensitivity to PTC bitterness among healthy Chinese college students in Hubei province. The association of TAS2R38 polymorphisms and PTC sensitivity with body mass index (BMI), food preference, and health status was also analyzed. A total of 320 healthy college students were enrolled (male: 133, female: 187; aged 18–23 years). The threshold value method was used to measure the perception of PTC bitterness, and a questionnaire was used to analyze dietary preferences and health status. Polymerase chain reaction (PCR) was used to analyze polymorphisms at three common TAS2R38 loci (rs713598, rs1726866, and rs10246939).ResultsIn our study population, 65.00% of individuals had medium sensitivity to the bitterness of PTC; in contrast, 20.94% were highly sensitive to PTC bitterness, and 14.06% were not sensitive. For the TAS2R38 gene, the PAV/PAV and PAV/AAI diplotypes were the most common (42.19% and 40.63%, respectively), followed by the homozygous AVI/AVI (8.75%) and PAV/AVI (5.00%) diplotypes.ConclusionThere was a significant correlation between the sensitivity to PTC bitterness and sex, but there was no correlation between the common diplotypes of TAS2R38 and gender. Polymorphisms in the TAS2R38 gene were associated with the preference for tea, but not with one’s native place, BMI, health status, or other dietary preferences. There was no significant correlation between the perception of PTC bitterness and one’s native place, BMI, dietary preference, or health status. We hope to find out the relationship between PTC sensitivity and TAS2R38 gene polymorphisms and dietary preference and health status of Chinese population through this study, providing relevant guidance and suggestions for dietary guidance and prevention of some chronic diseases in Chinese population.

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.

TAS2R38 polymorphisms, Helicobacter pylori infection and susceptibility to gastric cancer and premalignant gastric lesions.

Gastric cancer is worldwide the fourth more common cancer type by incidence, and the third by mortality. We analyzed three missense variants of TAS2R38 gene: rs713598 (A49P), rs1726866 (V262A), and rs10246939 (I296V). These variants and their combination in haplotypes (proline, alanine and valine/tasters or alanine, valine and isoleucine/nontasters) and diplotypes are responsible for individual differences in bitter perception. The single-nucleotide polymorphisms and the related phenotypes are known to be associated with susceptibility to Gram-negative bacterial infections, such as Helicobacter pylori , and with risk of various cancer types. An association between intermediate tasters (as defined by TAS2R38 diplotypes) and increased risk of gastric cancer was reported in a Korean population. We analyzed 2616 individuals of Latin American origin, representing the whole spectrum of lesions from gastritis to gastric cancer. Comparing cancer cases vs. noncancers we observed a decrease in risk associated with heterozygous carriers of rs10246939 ( P = 0.006) and rs1726866 ( P = 0.003) when compared with homozygotes of the more common allele. Also, the analysis of diplotypes/phenotypes reflected the same association, with super-tasters showing a borderline increased risk of developing gastric cancer compared to medium-tasters [odds ratio (OR) = 1.63; 95% confidence interval (CI), 1.04-2.56; P = 0.033]. Also, nontasters showed an increased risk when compared to medium-tasters although not reaching statistical significance (OR = 1.58; 95% CI, 0.80-2.87; P = 0.203). We also tested the interactions between the TAS2R38 genotypes and H. pylori cagA status in a subset of samples and found no interaction. In conclusion, our results suggest only a modest contribution of TAS2R38 gene genetic variability in gastric cancer etiology.

Predominant Qualities Evoked by Quinine, Sucrose, and Capsaicin Associate With PROP Bitterness, but not TAS2R38 Genotype.

Genetic variability in the ability to taste thiourea compounds has been studied for 80+ years. Over the last 3 decades, many studies have reported perceived intensity of concentrated propylthiouracil (PROP) associates with greater intensity from a broad range of stimuli, including nonbitter tastants, irritants, and retronasally delivered odorants. Thus, PROP phenotype has become a common measure of individual differences in orosensation. Much, but not all, of the phenotypic variation in PROP bitterness is explained by TAS2R38 polymorphisms. While differences in PROP bitterness are clearly due to genetic variation, mechanistically it is challenging to envision how this receptor (narrowly tuned to the N-C=S moiety) relates to overall orosensory response. Here, we report data for 200+ individuals who had been genotyped for TAS2R38 and phenotyped for PROP in a laboratory setting. Participants also reported the intensity of quinine, capsaicin, and sucrose on a general Labeled Magnitude Scale. Our data recapitulate earlier reports associating PROP bitterness with the intensity of the predominant qualities of sucrose, quinine, and capsaicin; however, we also find correlations between the intensities of sucrose, quinine, and capsaicin were much stronger with each other than with PROP. As expected, TAS2R38 diplotype did not associate with the intensity of sucrose, quinine, or capsaicin. The strength of PROP-capsaicin and PROP-sucrose relationships increased after grouping participants by TAS2R38 diplotype, with the greatest increases in association observed within homozygotes. Collectively, this suggests the suprathreshold intensity of PROP is a confounded phenotype that captures both genetic variation specific to N-C=S compounds and overall orosensation.

TAS2R38 Bitterness Receptor Genetic Variation and Risk of Gastrointestinal Neoplasm: A Meta-Analysis

Genetic variation in TAS2R38 bitterness taste receptor could alter the efficacy of molecular sensing, hence may be associated with cancer risk. Thus, we performed a meta-analysis to verify the association between the risk of gastrointestinal (GI) neoplasm and TAS2R38 genetic variation. Studies with TAS2R38 diplotype distribution and GI neoplasm phenotypes were searched from PubMed, EMBASE and SCOPUS, and five articles including eight studies were finally selected. The association between diplotype and neoplasm risk was estimated with summarized odds ratios (ORs) and 95% confidence intervals (CIs), applying of fixed- or random-effects models. The findings suggested TAS2R38 diplotype was not associated with GI neoplasms susceptibility [AVI vs. PAV: OR = 1.03 (95%CI: 0.97–1.09), AVI/PAV vs. PAV/PAV: OR = 1.05, (95%CI: 0.94–1.17), AVI/* vs. PAV/PAV: OR = 1.04 (95%CI: 0.94–1.16)]. Because of the presence of heterogeneity under the two genetic models (AVI/AVI vs. PAV/PAV and AVI/AVI vs. PAV/*), further subgroup analyses by ethnicity and neoplasm type were performed. However, results failed to show the neoplasm risk was altered by diplotype. In conclusion, the meta-analysis indicates that TAS2R38 diplotype minimally modified the GI neoplasm risk. Given the limited study size and resources, further well-designed and larger studies are required to validate the true effect of TAS2R38 polymorphisms on neoplasm risk.

TAS2R38 Predisposition to Bitter Taste Associated with Differential Changes in Vegetable Intake in Response to a Community-Based Dietary Intervention.

Although vegetable consumption associates with decreased risk for a variety of diseases, few Americans meet dietary recommendations for vegetable intake. TAS2R38 encodes a taste receptor that confers bitter taste sensing from chemicals found in some vegetables. Common polymorphisms in TAS2R38 lead to coding substitutions that alter receptor function and result in the loss of bitter taste perception. Our study examined whether bitter taste perception TAS2R38 diplotypes associated with vegetable consumption in participants enrolled in either an enhanced or a minimal nutrition counseling intervention. DNA was isolated from the peripheral blood cells of study participants (N = 497) and analyzed for polymorphisms. Vegetable consumption was determined using the Block Fruit and Vegetable screener. We tested for differences in the frequency of vegetable consumption between intervention and genotype groups over time using mixed effects models. Baseline vegetable consumption frequency did not associate with bitter taste diplotypes (P = 0.937), however after six months of the intervention, we observed an interaction between bitter taste diplotypes and time (P = 0.046). Participants in the enhanced intervention increased their vegetable consumption frequency (P = 0.020) and within this intervention group, the bitter non-tasters and intermediate-bitter tasters had the largest increase in vegetable consumption. In contrast, in the minimal intervention group, the bitter tasting participants reported a decrease in vegetable consumption. Bitter-non tasters and intermediate-bitter tasters increased vegetable consumption in either intervention more than those who perceive bitterness. Future precision medicine applications could consider genetic variation in bitter taste perception genes when designing dietary interventions.

In Vivo Biofilm Formation, Gram-Negative Infections and TAS2R38 Polymorphisms in CRSw NP Patients.

Among the predisposing factors implicated in the immune response to airway bacterial infections, genetic variations of the bitter taste receptor TAS2R38, which is expressed in the cilia of the human sinonasal epithelial cells, seem to be associated with susceptibility to chronic rhinosinusitis (CRS) and in vitro biofilm formation. Polymorphisms in TAS2R38 generate two common haplotypes: the nonfunctional AVI (Alanine, Valine, Isoleucine) and the functional PAV (Proline, Alanine, Valine) alleles, with the latter protecting against gram-negative sinonasal infections. The aim of this study is to investigate for the first time the relevance of TAS2R38 genetic variants in the susceptibility to bacterial infections associated with in vivo biofilm formation in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. A prospective study on 100 adult patients undergoing functional endoscopic sinus surgery (FESS) for CRSwNP. Propylthiouracile (PROP) testing and TAS2R38 genotyping were applied to characterize patients for receptor functionality. Sinonasal mucosa samples were processed for microbiological examination and biofilm detection. The nonfunctional genotype is more frequent among CRS patients than in the general population (25% vs. 18.4%, P = 0.034). Airway gram-negative infections are primarily associated with the AVI haplotype (88.9% vs. 11.1% PAV/PAV-functional genotype, P = 0.023). Biofilm formation is prevalent in CRS patients with the AVI nontaster phenotype (62.5% vs. 33.3% PAV taster or supertaster phenotype, P = 0.05). Our findings confirm an inverse correlation between TAS2R38 functionality and gram-negative infections in Italian patients with CRSwNP. In addition, for the first time we demonstrated a relationship between in vivo microbial biofilm and TAS2R38 receptor variants. 2b. Laryngoscope, 128:E339-E345, 2018.

Is food refusal in autistic children related to TAS2R38 genotype?

A variation of the gene TAS2R38, associated with bitter taste sensitivity, can cause a different perception of some foods. In particular, some children are hypersensitive to bitterness and show a more restricted repertoire of accepted foods. We evaluate bitter sensitivity in ASD children with or without food selectivity, through a simple bitter taste test with edible strips. The results show that food refusal in ASD children can be mediated by bitter taste sensitivity thus suggesting that the bitter sensitivity test may be used as a device to orientate tailored food proposals for the practical management of food selectivity in ASD.

Flavones modulate respiratory epithelial innate immunity: Anti-inflammatory effects and activation of the T2R14 receptor

Chronic rhinosinusitis has a significant impact on patient quality of life, creates billions of dollars of annual healthcare costs, and accounts for ∼20% of adult antibiotic prescriptions in the United States. Because of the rise of resistant microorganisms, there is a critical need to better understand how to stimulate and/or enhance innate immune responses as a therapeutic modality to treat respiratory infections. We recently identified bitter taste receptors (taste family type 2 receptors, or T2Rs) as important regulators of sinonasal immune responses and potentially important therapeutic targets. Here, we examined the immunomodulatory potential of flavones, a class of flavonoids previously demonstrated to have antibacterial and anti-inflammatory effects. Some flavones are also T2R agonists. We found that several flavones inhibit Muc5AC and inducible NOS up-regulation as well as cytokine release in primary and cultured airway cells in response to several inflammatory stimuli. This occurs at least partly through inhibition of protein kinase C and receptor tyrosine kinase activity. We also demonstrate that sinonasal ciliated epithelial cells express T2R14, which closely co-localizes (<7 nm) with the T2R38 isoform. Heterologously expressed T2R14 responds to multiple flavones. These flavones also activate T2R14-driven calcium signals in primary cells that activate nitric oxide production to increase ciliary beating and mucociliary clearance. TAS2R38 polymorphisms encode functional (PAV: proline, alanine, and valine at positions 49, 262, and 296, respectively) or non-functional (AVI: alanine, valine, isoleucine at positions 49, 262, and 296, respectively) T2R38. Our data demonstrate that T2R14 in sinonasal cilia is a potential therapeutic target for upper respiratory infections and that flavones may have clinical potential as topical therapeutics, particularly in T2R38 AVI/AVI individuals.

Genetic Variation in the TAS2R38 Bitter Taste Receptor and Smoking Behaviors.

Common TAS2R38 taste receptor gene variants specify the ability to taste phenylthiocarbamide (PTC), 6-n-propylthiouracil (PROP) and structurally related compounds. Tobacco smoke contains a complex mixture of chemical substances of varying structure and functionality, some of which activate different taste receptors. Accordingly, it has been suggested that non-taster individuals may be more likely to smoke because of their inability to taste bitter compounds present in tobacco smoke, but results to date have been conflicting. We studied three cohorts: 237 European-Americans from the state of Georgia, 1,353 European-Americans and 2,363 African-Americans from the Dallas Heart Study (DHS), and 4,973 African-Americans from the Dallas Biobank. Tobacco use data was collected and TAS2R38 polymorphisms were genotyped for all participants, and PTC taste sensitivity was assessed in the Georgia population. In the Georgia group, PTC tasters were less common among those who smoke: 71.5% of smokers were PTC tasters while 82.5% of non-smokers were PTC tasters (P = 0.03). The frequency of the TAS2R38 PAV taster haplotype showed a trend toward being lower in smokers (38.4%) than in non-smokers (43.1%), although this was not statistically significant (P = 0.31). In the DHS European-Americans, the taster haplotype was less common in smokers (37.0% vs. 44.0% in non-smokers, P = 0.003), and conversely the frequency of the non-taster haplotype was more common in smokers (58.7% vs. 51.5% in non-smokers, P = 0.002). No difference in the frequency of these haplotypes was observed in African Americans in either the Dallas Heart Study or the Dallas Biobank. We conclude that TAS2R38 haplotypes are associated with smoking status in European-Americans but not in African-American populations. PTC taster status may play a role in protecting individuals from cigarette smoking in specific populations.

Genetic Variation in the TAS2R38 Bitter Taste Receptor and Gastric Cancer Risk in Koreans.

The human TAS2R38 gene encodes a bitter taste receptor that regulates the bitterness perception and differentiation of ingested nutritional/poisonous compounds in the oral cavity and gastrointestinal tract. TAS2R38 gene variants are associated with alterations in individual sensitivity to bitter taste and food intake; hence, these genetic variants may modify the risk for diet-related diseases, including cancer. However, little is known about the association between TAS2R38 polymorphisms and gastric cancer susceptibility. The present case-control study examined the influence of TAS2R38 polymorphisms on food intake and determined whether they predict gastric cancer risk in Koreans. A total of 1,580 subjects, including 449 gastric cancer cases, were genotyped for TAS2R38 A49P, V262A, I296V and diplotypes. Dietary data were analysed to determine the total consumption of energy, fibre, vegetables, fruits, sweets, fats, alcohol and cigarettes. TAS2R38 diplotype was not associated with food, alcohol or cigarette consumption, either independent or dependent of gastric cancer phenotype. However, the PAV/AVI diplotype significantly increased gastric cancer risk (adjusted odds ratio: 1.513; 95% confidence interval: 1.148–1.994) independent of dietary intake. Findings suggest that TAS2R38 may be associated with the risk for gastric cancer in Koreans, although the TAS2R38 diplotype did not influence dietary intake.

Implications of Taste Receptor Polymorphisms in Dietary Interventions: TAS2R38 Polymorphisms Associate with Changes in Vegetable Intake

Few Americans meet consumption recommendations for dark green and orange vegetables that are strongly associated with reduced risk of chronic diseases. The ability to detect propylthiouricil, or PROP, is linked to vegetable preference and frequency of vegetable consumption. The TAS2R38 gene encodes a g‐protein coupled receptor that binds PROP and phenylthiocarbamide (PTC). Both PROP and PTC resemble natural bitter compounds found in green vegetables. Our study examined if allele status of a single nucleotide polymorphism (SNP, rs10246939) in the TAS2R38 gene associated with bitter taste perception in vegetables affects: 1) the frequency of reported vegetable consumption prior to, and 2) the change in frequency of vegetable consumption after six months of either an enhanced or a minimal nutrition counseling intervention within the Heart Healthy Lenoir (HHL) study. SNP status was obtained from HHL participants either through DNA isolated from peripheral blood cells using the Infinium Human Omni Express Exome+ BeadChip (Illumina) and standard imputation methods for missing genotypes. Frequency of vegetable intake and covariates (age, gender, race, income) were available for 491 and 373 participants at baseline and at the six‐month follow‐up, respectively. We found that bitter taste genotype at rs10246939 was not associated with vegetable intake at baseline (p=0.90). After the dietary intervention we found a significant difference in frequency of vegetable intake from baseline to follow‐up between groups defined by SNP status (p&lt;0.001); participants that were heterozygous or homozygous for the bitter taste genotype in rs10246939 consumed fewer vegetables suggesting that dietary intervention success regarding dark green vegetable intake may be influenced by underlying genetic differences in taste perceptions. We completed imputation of all three bitter taste receptor gene clusters (chromosomes 5, 7, and 12) within our dietary intervention cohort as well as a plasma carotenoid panel and are currently performing additional association analyses between these additional bitter taste receptor polymorphisms, carotenoid levels, and reported vegetable intake. Our results suggest that bitter taste genetic variation could be utilized in designing interventions to promote healthy eating.Support or Funding Information1P50HL105184‐01 National Heart, Lung, and Blood Institute

Receptor Polymorphism and Genomic Structure Interact to Shape Bitter Taste Perception.

The ability to taste bitterness evolved to safeguard most animals, including humans, against potentially toxic substances, thereby leading to food rejection. Nonetheless, bitter perception is subject to individual variations due to the presence of genetic functional polymorphisms in bitter taste receptor (TAS2R) genes, such as the long-known association between genetic polymorphisms in TAS2R38 and bitter taste perception of phenylthiocarbamide. Yet, due to overlaps in specificities across receptors, such associations with a single TAS2R locus are uncommon. Therefore, to investigate more complex associations, we examined taste responses to six structurally diverse compounds (absinthin, amarogentin, cascarillin, grosheimin, quassin, and quinine) in a sample of the Caucasian population. By sequencing all bitter receptor loci, inferring long-range haplotypes, mapping their effects on phenotype variation, and characterizing functionally causal allelic variants, we deciphered at the molecular level how a subjects’ genotype for the whole-family of TAS2R genes shapes variation in bitter taste perception. Within each haplotype block implicated in phenotypic variation, we provided evidence for at least one locus harboring functional polymorphic alleles, e.g. one locus for sensitivity to amarogentin, one of the most bitter natural compounds known, and two loci for sensitivity to grosheimin, one of the bitter compounds of artichoke. Our analyses revealed also, besides simple associations, complex associations of bitterness sensitivity across TAS2R loci. Indeed, even if several putative loci harbored both high- and low-sensitivity alleles, phenotypic variation depended on linkage between these alleles. When sensitive alleles for bitter compounds were maintained in the same linkage phase, genetically driven perceptual differences were obvious, e.g. for grosheimin. On the contrary, when sensitive alleles were in opposite phase, only weak genotype-phenotype associations were seen, e.g. for absinthin, the bitter principle of the beverage absinth. These findings illustrate the extent to which genetic influences on taste are complex, yet arise from both receptor activation patterns and linkage structure among receptor genes.

Association of a novel TAS2R38 haplotype with alcohol intake among Mexican-Mestizo population

Background. Alcohol intake has been associated with the bitter taste receptor T2R38. TAS2R38 gene expresses two common haplotypes: PAV and AVI. It has been reported that AVI homozygotes consume more alcohol than heterozygotes and PAV homozygotes. The aim of this study was to determine the prevalence of the TAS2R38 haplotypes among Mexican-Mestizo population and to analyze its association with alcohol intake.Material and methods. In a cross-sectional study, a total of 375 unrelated Mestizo individuals were genotyped for TAS2R38 polymorphisms (A49P, V262A and I296V) by a Real-Time PCR System (TaqMan). Haplotype frequencies were calculated. Association of TAS2R38 haplotypes with alcohol intake was estimated in drinkers (DRS) and nondrinkers (NDRS).Results. Two haplotypes accounted for over 96% of all haplotypes (AVV, 60%, and PAI, 36.5%). The frequency of AVV homozygotes was significantly higher in DRS than NDRS (47.2 vs. 32.2%, respectively; p < 0.05). Additionally, the AVV/AVV genotype was associated with alcohol intake when compared with heterozygotes and PAI homozygotes (OR = 1.79, 95% CI 1.13-2.84, p < 0.05 and OR = 2.23, 95% CI 1.11-4.48; p < 0.05, respectively).Conclusions. In conclusion, two TAS2R38 haplotypes (AVV and PAI) prevailed in Mexican-Mestizo population. The novel AVV haplotype was associated with alcohol intake. The high prevalence of this allelic profile in our population could help to explain, at least in part, the preference for alcohol among the Mexicans.

Probiotic yoghurt and incidence of diarrhoea in children: A double blind, randomised, controlled trial

Probiotic yoghurt and incidence of diarrhoea in children: A double blind, randomised, controlled trial