TAS2R38 Haplotypes 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...

Differential Activation of TAS2R4 May Recover Ability to Taste Propylthiouracil for Some TAS2R38 AVI Homozygotes.

Bitterness from phenylthiocarbamide and 6-n-propylthiouracil (PROP) varies with polymorphisms in the TAS2R38 gene. Three SNPs form two common (AVI, PAV) and four rare haplotypes (AAI, AAV, PVI, and PAI). AVI homozygotes exhibit higher detection thresholds and lower suprathreshold bitterness for PROP compared to PAV homozygotes and heterozygotes, and these differences may influence alcohol and vegetable intake. Within a diplotype, substantial variation in suprathreshold bitterness persists, and some AVI homozygotes report moderate bitterness at high concentrations. A second receptor encoded by a gene containing a functional polymorphism may explain this. Early work has suggested that PROP might activate TAS2R4 in vitro, but later work did not replicate this. Here, we identify three TAS2R4 SNPs that result in three diplotypes-SLN/SLN, FVS/SLN, and FVS/FVS-which make up 25.1%, 44.9%, and 23.9% of our sample. These TAS2R4 haplotypes show minimal linkage disequilibrium with TAS2R38, so we examined the suprathreshold bitterness as a function of both. The participants (n = 243) rated five PROP concentrations in duplicate, interleaved with other stimuli. As expected, the TAS2R38 haplotypes explained ~29% (p < 0.0001) of the variation in the bitterness ratings, with substantial variation within the haplotypes (AVI/AVI, PAV/AVI, and PAV/PAV). Notably, the TAS2R4 diplotypes (independent of the TAS2R38 haplotypes) explained ~7-8% of the variation in the bitterness ratings (p = 0.0001). Given this, we revisited if PROP could activate heterologously expressed TAS2R4 in HEK293T cells, and calcium imaging indicated 3 mM PROP is a weak TAS2R4 agonist. In sum, our data are consistent with the second receptor hypothesis and may explain the recovery of the PROP tasting phenotype in some AVI homozygotes; further, this finding may potentially help explain the conflicting results on the TAS2R38 diplotype and food intake.

Bitter taste sensitivity and frequency of bitter food intake in healthy Australian adults: a cross-sectional, mixed-methods study

Bitter taste perception plays a dual role in human nutrition and evolutionary biology; being identifiable in nutrient-dense foods such as cruciferous vegetables and historically signalled toxic compounds. The TAS2R38 gene, part of the taste 2 receptor family, is central to individual differences in bitter taste perception(1). While genetic variations are influential, dietary habits and food preparation also impact taste perception. However, research investigating the interplay between these factors and genetic variations in influencing bitter taste sensitivity and food intake is limited. This study aimed to elucidate the relationship between bitter taste sensitivity and TAS2R38 haplotype variations in the context of bitter food consumption among Australian adults. A cross-sectional, mixed-methods study was conducted. Healthy adults who had maintained a stable diet for at least three months were eligible. Data collection was via an online survey (REDCap), capturing self-reported demographics, dietary patterns specific to bitter foods including metrics of bitter food avoidance, frequency, liking and perceived healthfulness, alongside a Dietary Quality Index (DQI) derived from a food frequency questionnaire(2). Bitter taste sensitivity was assessed using self-reported intensity perceptions of 6-n-propylthiouracil (PROP) taste strips(3). Genotyping was conducted via TaqMan qPCR assays on DNA extracted from buccal swabs to ascertain TAS2R38 haplotypes. Data analysis utilised Analysis of Covariance (ANCOVA) and regression models, with all tests adjusted for confounding variables such as gender, age, and smoking status. A total of 222 participants (47.5 ± 17.7 years; 86% female; BMI 27.3 ± 7.1 kg/m2) completed the study. PROP sensitivity was strongly correlated with TAS2R38 haplotype, with supertasters predominantly having PAV/PAV, medium tasters with PAV/AVI, and non-tasters with AVI/AVI (p = 0.002). However, no relationship was observed between PROP sensitivity and either the frequency, liking, or avoidance of bitter foods (p&gt;0.05). DQI was significantly related to bitter food consumption; individuals in the lowest DQI quintile consumed bitter foods more frequently than those in the third (p = 0.007) and top quintiles (p = 0.001). The perceived healthfulness of bitter foods was significantly higher in those with AVI/AVI haplotypes (non-tasters) compared to those with PAV/AVI (medium tasters) (p = 0.001). Counterintuitively, participants who reported greater enjoyment of bitter tastes consumed bitter foods less frequently (p&lt;0.001). Our study confirms that TAS2R38 variants are predictive of PROP taste sensitivity, consistent with literature that identifies PAV/PAV individuals as supertasters. However, neither PROP sensitivity nor TAS2R38 haplotype influenced bitter food frequency or preference consumption patterns. Interestingly, those with lower Dietary Quality Index scores and less enjoyment of bitter taste consumed bitter foods more often. These observations highlight the need to investigate other factors influencing bitter food intake, such as additional sensory characteristics or psychological and behavioural aspects.

TAS2R38 haplotypes, COVID-19 infection, and symptomatology: a cross-sectional analysis of data from the Canadian Longitudinal Study on Aging

The TAS2R38 gene is well known for its function in bitter taste sensitivity, but evidence also suggests a role in innate immunity. TAS2R38 may be relevant in coronavirus disease 2019 (COVID-19), but research findings are inconsistent. The objective of this study was to explore whether common TAS2R38 haplotypes are associated with COVID-19 infection and symptomatology in the Canadian Longitudinal Study on Aging (CLSA). Data from the CLSA COVID-19 Questionnaire and Seroprevalence sub-studies were utilized with CLSA genetic data for common TAS2R38 haplotypes related to bitter taste sensitivity. Haplotypes were categorized into three diplotype groups: [P]AV homozygotes, [P]AV/[A]VI heterozygotes, and [A]VI homozygotes. No significant differences were observed between diplotypes and COVID-19 infection frequency. Among self-reported COVID-19 cases (n = 76), and in uncorrected exploratory analyses, heterozygotes were less likely to report experiencing sinus pain compared to [P]AV homozygotes. Among seroprevalence-confirmed cases (n = 177), [A]VI homozygotes were less likely to report experiencing a sore/scratchy throat compared to [P]AV homozygotes. However, both observations were non-significant upon correction for multiple testing. In this study, TAS2R38 haplotypes were not significantly associated with COVID-19 infection or symptomatology. Nevertheless, in light of some exploratory patterns and conflicting evidence, additional research is warranted to evaluate links between TAS2R38 and innate immunity.

The Bittersweet Symphony of COVID-19: Associations between TAS1Rs and TAS2R38 Genetic Variations and COVID-19 Symptoms.

The innate immune system is crucial in fighting SARS-CoV-2 infection, which is responsible for coronavirus disease 2019 (COVID-19). Therefore, deepening our understanding of the underlying immune response mechanisms is fundamental for the development of novel therapeutic strategies. The role of extra-oral bitter (TAS2Rs) and sweet (TAS1Rs) taste receptors in immune response regulation has yet to be fully understood. However, a few studies have investigated the association between taste receptor genes and COVID-19 symptom severity, with controversial results. Therefore, this study aims to deepen the relationship between COVID-19 symptom presence/severity and TAS1R and TAS2R38 (TAS2Rs member) genetic variations in a cohort of 196 COVID-19 patients. Statistical analyses detected significant associations between rs307355 of the TAS1R3 gene and the following COVID-19-related symptoms: chest pain and shortness of breath. Specifically, homozygous C/C patients are exposed to an increased risk of manifesting severe forms of chest pain (OR 8.11, 95% CI 2.26-51.99) and shortness of breath (OR 4.83, 95% CI 1.71-17.32) in comparison with T/C carriers. Finally, no significant associations between the TAS2R38 haplotype and the presence/severity of COVID-19 symptoms were detected. This study, taking advantage of a clinically and genetically characterised cohort of COVID-19 patients, revealed TAS1R3 gene involvement in determining COVID-19 symptom severity independently of TAS2R38 activity, thus providing novel insights into the role of TAS1Rs in regulating the immune response to viral infections.

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.

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.

TAS2R38 Haplotype Predicts 24-Hour Urinary Sodium Excretion in Patients With Heart Failure and Their Family Caregivers.

Adherence to a low-sodium diet is essential to self-care of heart failure (HF). Genetic determinants of preference for high-sodium foods may impede adherence but have not been well-studied. Our purpose was to examine if TAS2R38 haplotype predicted salt taste sensitivity and dietary sodium intake among patients with HF. This pilot study used baseline data from a large interventional randomized control trial to support adherence to a low-sodium diet in patients with HF and their family caregivers. Participants were tested for salt taste sensitivity and provided a 24-hour urinary sodium sample and a blood sample for DNA analysis at baseline. Fungiform papillae were counted. χ2 Test and 1-way analysis of variance were used to compare haplotype groups. Linear regression was performed to examine predictors of salt taste sensitivity and 24-hour urinary sodium excretion, controlling for age, gender, ethnicity, smoking status, and fungiform papillae density. There were 42 patients with HF and their family caregivers (age, 64.6 ± 13.4 years, 46.5% male, 97.7% white, and 90.7% nonsmoker). Pronine-alanine-valine homozygous haplotype predicted lower urinary sodium excretion (b = -1780.59, t41 = -2.18, P = .036), but genotype was not a significant predictor of salt taste sensitivity. The results of our study partially supported our hypothesis that PAV homozygous haplotype predicts 24-hour urinary sodium excretion. With our small sample size, more research is needed. Understanding genetic influences on taste can lead to development of educational interventions tailored to patients with HF and their family caregivers to better support dietary adherence.

Cystic fibrosis transmembrane conductance regulator function, not TAS2R38 gene haplotypes, predict sinus surgery in children and young adults with cystic fibrosis.

Chronic rhinosinusitis symptomatology begins in early childhood individuals with cystic fibrosis (CF). Cystic fibrosis transmembrane conductance regulator (CFTR) function contributes to sinus development and disease. Genetic variants of the bitter taste receptor TAS2R38 have been suggested to contribute to sinus disease severity in individuals without CF. Our objective was to explore whether functional TAS2R38 haplotypes and CFTR function are associated with sinus disease or the need for sinus surgery in individuals with CF. We conducted a retrospective study using prospectively collected data from the CF Twin-Sibling Study. The function of CFTR was assessed via chloride conductance. Genotyping of the TAS2R38 gene identified patients who were homozygous for the functional haplotype, heterozygous, or homozygous for nonfunctional haplotypes. Clustered multivariate logistic regression was performed, controlling for sex and family relationship. A total of 1291 patients were evaluated. Patients with ≤1% CFTR function were 1.56 times more likely to require sinus surgery than those with >1% CFTR function (p = 0.049). CFTR function did not correlate significantly with the presence of sinus disease (p = 0.30). In addition, there were no statistically significant differences in diagnosis of sinus disease or need for sinus surgery between patients with functional and nonfunctional TAS2R38 haplotypes. CFTR function correlates with need for sinus surgery, whereas TAS2R38 function does not appear to contribute to sinus disease or the need for sinus surgery in patients with CF.

Functional divergence of the bitter receptor TAS2R38 in Sulawesi macaques.

Bitter perception is mediated by G protein‐coupled receptors TAS2Rs and plays an important role in avoiding the ingestion of toxins by inducing innate avoidance behavior in mammals. One of the best‐studied TAS2Rs is TAS2R38, which mediates the perception of the bitterness of synthetic phenylthiocarbamide (PTC). Previous studies of TAS2R38 have suggested that geographical separation enabled the independent divergence of bitter taste perception. The functional divergence of TAS2R38 in allopatric species has not been evaluated. We characterized the function of TAS2R38 in four allopatric species of Sulawesi macaques on Sulawesi Island. We found variation in PTC taste perception both within and across species. In most cases, TAS2R38 was sensitive to PTC, with functional divergence among species. We observed different truncated TAS2R38s that were not responsive to PTC in each species of Macaca nigra and M. nigrescens due to premature stop codons. Some variants of intact TAS2R38 with an amino acid substitution showed low sensitivity to PTC in M. tonkeana. Similarly, this intact TAS2R38 with PTC‐low sensitivity has also been found in humans. We detected a shared haplotype in all four Sulawesi macaques, which may be the ancestral haplotype of Sulawesi macaques. In addition to shared haplotypes among Sulawesi macaques, other TAS2R38 haplotypes were species‐specific. These results implied that the variation in TAS2R38 might be shaped by geographical patterns and local adaptation.OPEN RESEARCH BADGES This article has earned an Open Data Badge for making publicly available the digitally‐shareable data necessary to reproduce the reported results. The data is available at https://doi.org/10.5061/dryad.908jf3r.

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.

Genetic variation in bitter taste receptor gene TAS2R38, PROP taster status and their association with body mass index and food preferences in Indian population

Polymorphisms in bitter taste receptor gene TAS2R38 alter the ability to sense the intensity of bitterness of phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP). Genetic variation in sensitivity towards PTC and PROP may affect food preferences and susceptibility to certain diseases. This is the first study aimed at investigating frequency and distribution of TAS2R38 haplotypes in an Indian cohort. Additionally, we studied the association of TAS2R38 and PROP taster status with BMI and food preference. Three hundred and ninety three healthy adults who were 19–55years of age were selected as a convenience sample from 4 geographical regions of India. Single nucleotide polymorphisms (SNPs) of TAS2R38 (rs713598, s1726866 and rs10246939) were analyzed using polymerase chain reaction-restriction fragment length polymorphism. The prevalence of PAV/PAV diplotype was 9.9% and that of AVI/AVI diplotype was 43.76% among this Indian population. PROP status was determined on the basis of its threshold concentration of detecting bitterness, as evaluated by one-solution test. The PROP status revealed 25.95% supertasters, 32.06% medium tasters and 41.98% non-tasters (NT). BMI neither significantly (p>0.05) correlated with TAS2R38 genotypes nor with PROP taster status. Food preferences did not significantly (p>0.05) correlate with TAS2R38 diplotypes or PROP phenotypes.

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 variations of the bitter taste receptor TAS2R38 are associated with obesity and impact on single immune traits.

Changes in genetic variations affecting the taste receptor, type 2, member 38 (TAS2R38) may identify the interacting mechanism leading to obesity and potential associations with proteins partaking in innate immunity, such as surfactant protein D (SPD) and mannan-binding lectin (MBL). We evaluated haplotypes of the bitter-taste receptor TAS2R38 in an identification sample of 210 women in different weight conditions, including anorexia nervosa and obesity. The association with SPD and MBL was tested in an independent sample picturing general population (n = 534). The relationship with obesity was validated in an extended final sample of 1319 participants. In the sample comprised of women in extreme weight conditions, increased obesity was identified in AVI/AVI subjects (OR = 2.5 [1.06-6.11], p = 0.035). In the sample picturing general population, increased SPD and MBL concentrations were found in nonsmoking AVI carriers. In this cohort, smoking and obesity blunted associations between TAS2R38 haplotypes and SPD and MBL. In the extended sample, the association of AVI/AVI haplotypes with increased obesity was also identified (OR = 1.4 [0.99/1.85], p = 0.049), being more robust in subjects aged <40 years (OR = 1.9 [1.06/3.42], p = 0.031). Current data reinforce the impact of TAS2R38 gene on phenotypic and clinical outputs affecting obesity, showing significant associations with extreme weight conditions (i.e., obesity and anorexia nervosa), and changes in both olfactory capacity and immune traits.

Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal.

The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes.

Rare haplotypes of the gene TAS2R38 confer bitter taste sensitivity in humans.

BackgroundThe TAS2R38 gene is widely responsible for the well-known bimodal response to a family of bitter chemicals which includes 6-n-propylthiouracial (PROP). There are two common haplotypes of this gene, the recessive AVI and the dominant PAV, both of which are well studied. Conversely, the role of rare TAS2R38 haplotypes on bitter taste sensitivity has been notoriously difficult to study due to small sample sizes. Here we present PROP sensitivity data of 97 individuals that have been observed to carry rare haplotypes (AAV, AAI, PAI, PVI) of the TAS2R38 gene.ResultsParticipants rated their bitter taste perception to a PROP filter disc then provided a buccal DNA sample from which the TAS2R38 gene was sequenced and analyzed. We found the prevalence of the PAV haplotype to be 42.3 %, AVI 53.1 %, AAV 2.5 %, AAI 1.2 %, PAI 0.8 % and PVI 0.1 %. We found that the AAI, AAV, and PAI haplotypes present intermediate taste sensitivity.ConclusionsThese data are further evidence that bitter taste sensitivity to PROP exists as a broad range, and not exclusively as nontasters, medium tasters, and supertasters.

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.

A novel application of breath hydrogen and methane monitoring in nutritional science

s / Journal of Nutrition & Intermediary Metabolism 1 (2014) 1e55 14 I296V; rs10246939) and grouped by haplotype. Serum and red cell folate levels (chemiluminescent immunoassay) and estimated folate intake (food frequency questionnaires) were determined. 6-n-propylthiouracil solutions were used to determine bitter taste phenotype (“taster”/”nontaster”). Differences between groups were assessed by t-tests, c2 tests and RR of AP. Results: TAS2R38 haplotype significantly, but only partially predicted taster phenotype (r 1⁄4 0.43, c21⁄435.5, p 50% improvement of symptoms, was assessed. Difference between the groups was tested via Fishers exact test. Results: Of 157 women with IBS, 56 (35%) had a concurrent diagnosis of endometriosis. The median age of those with endometriosis was 32 as opposed to those without where median age was 39 (p 1⁄4 0.014). However, response was reported in 71% with endometriosis compared with 47% of those without endometriosis (p 1⁄4 0.004). Conclusions: The high rate of response to a LFD suggests that this approach should be added to the repertoire of management strategies for endometriosis. Why the response was poorer in those without endometriosis was not clear. Funding source(s): N/A. POSTPRANDIAL NUTRIGENOMIC PATHWAY ANALYSIS OF ADIPOSE TISSUE IN MEN WITH METABOLIC SYNDROME (METS) A.L. Dordevic , M.P. Bonham , A.E. Larsen , P. Gran , A.J. Sinclair , J.B. Jowett , N. Konstantopoulos , D. Cameron-Smith . 1 School of Exercise & Nutritional Science, Deakin University, Australia; Department Nutrition & Dietetics, Monash University, Australia; Metbolic Research Unit, Deakin University, Australia; Genomic & Systems Biology, Baker IDI, VIC, Australia; 5 Liggins Institute, Auckland University, NZ, New Zealand E-mail: aimee.dordevic@monash.edu (A.L. Dordevic) Background/Aims: Profiling the transcriptomic regulation of adipose tissue (AT) by dietary manipulation in MetS will elucidate therapeutic and nutritional targets for chronic disease management. Methods: Seventeen men (8 control; 9 MetS) were recruited to participate in a controlled randomised, single-blinded crossover single meal study. Participants consumed either a saturated fatty acid (FA)-rich breakfast or an unsaturated FA-rich breakfast. AT biopsies were taken at baseline (0 h), and 4 h following each test meal. Global gene expression profiling of the AT was performed using Illumina HumanWG-6 v3 microarray chips followed by gene set enrichment analysis (GSEA) using DAVID software. Pathways were considered significant with Expression Analysis Systematic Explorer (EASE) score < 0.05 and a false discovery rate (FDR) value < 0.05. Results: Two pathways that were differentially regulated in MetS compared to control AT at baseline were also enriched by the following meal consumption. The Lysosome pathway was up-regulated (p < 0.001) and the Ribosome pathway was down-regulated (p < 0.001) in MetS AT compared with controls at baseline. Control AT exhibited enrichment of the Lysosome pathway with the SFA meal (p1⁄4 0.001) and MetS AT showed enrichment of the Ribosome pathway after the UFA meal (p 1⁄4 0.02). Conclusions: Lysosome and Ribosome pathways are impaired in MetS AT and can be manipulated by alterations in meal composition. This finding is important in the discovery of potential nutritional targets for chronic metabolic disease. Funding source(s): Dairy Health & Nutrition Consortium (DHNC). REDUCED FODMAPS IN GLUTEN-FREE GRAINS MAY EXPLAIN THE IMPROVED SYMPTOMS IN PEOPLE WITH IBS FOLLOWING A GLUTENFREE DIET J.G. Muir , J. Mills , D. Suter , F. Bekes , K. Liels , C.K. Yao , P.R. Gibson . Department of Gastroenterology, Central Clinical School, Monash University, Australia; George Weston Foods Ltd, North Ryde, NSW, Australia E-mail: Jane.Muir@monash.edu (J.G. Muir) Background/Aims: Individuals with IBS blame gluten-containing grains for triggering gastrointestinal symptoms. Another component of grains that requires consideration is the FODMAPs mostly fructans and galacto-oligsaccharides (GOS). We aim to analyse the gluten and FODMAP content of 22

The gustin (CA6) gene polymorphism, rs2274333 (A/G), is associated with fungiform papilla density, whereas PROP bitterness is mostly due to TAS2R38 in an ethnically-mixed population

PROP responsiveness is associated with TAS2R38 haplotypes and fungiform papilla density. Recently, we showed that a polymorphism in the gene coding for the salivary trophic factor, gustin (CA6), affects PROP sensitivity by acting on cell growth and fungiform papillae maintenance, in a genetically homogeneous cohort. Since population homogeneity can lead to over estimation of gene effects, the primary aim of the present work was to confirm gustin's role in PROP bitterness intensity and fungiform papillae density in a genetically diverse population. Eighty subjects were genotyped for both genes by PCR techniques. PROP responsiveness was assessed by a filter paper method and fungiform papilla density was determined in each subject. As expected, PROP bitterness ratings were lower in individuals with the AVI/AVI diplotype of TAS2R38 than in individuals with PAV/PAV and PAV/AVI diplotypes. However, no differences in PROP bitterness among genotypes of the gustin gene, and no differences in the density of fungiform papillae related to TAS2R38 diplotype were found. In contrast, the density of fungiform papillae decreased as the number of minor (G) alleles at the gustin locus increased. In addition, the distribution of TAS2R38 genotypes within each gustin genotype group showed that the occurrence of recessive alleles at both loci was infrequent in the present sample compared to other populations. These findings confirm that papillae density is associated with gustin gene polymorphism, rs2274333 (A/G), in an ancestrally heterogeneous population, and suggest that variations in the frequency of allele combinations for these two genes could provide a salient explanation for discrepant findings for gustin gene effects across populations.

The Associations between 6-n-Propylthiouracil (PROP) Intensity and Taste Intensities Differ by TAS2R38 Haplotype

Background/Aims: The influence of TAS2R38 haplotype on the relationship between the perceived intensity of propylthiouracil (PROP) and the basic tastes of salt, sweet, sour, and bitter (quinine) was evaluated in the Beaver Dam Offspring Study. Methods: Genotyping was performed on 1,670 participants aged ≥45 years (mean age = 54.4; range = 45-84), and suprathreshold taste intensity was measured using filter paper disks and a general labeled magnitude scale (0-100). Results: Among those with taste intensity data and the PAV or AVI haplotype (n = 1,258), the mean perceived intensity of PROP was 37.3 (SD = 30.0), but it varied significantly (p < 0.0001) by diplotype (PAV/PAV = 60.1; PAV/AVI = 46.5; AVI/AVI = 14.4). PROP intensity was correlated with the basic taste intensities (salt: r = 0.22; sweet: r = 0.25; sour: r = 0.21; quinine bitterness: r = 0.38; p < 0.001 for all tastes); however, a significant effect modification of the PROP-taste intensity relationships by TAS2R38 diplotype was observed. There was a stronger association between PROP and each of the basic tastes in the PAV/PAV diplotype group than in the other groups. Conclusions: Directly measuring the perceived intensity of the 4 tastes, rather than using PROP intensity as an indicator of taste responsiveness, is recommended for studies of taste perception.