TAS2R38 Research Articles

Taste receptor T1R3 regulates testosterone synthesis via the cAMP-PKA-SP1 pathway in testicular Leydig cells

Taste receptor type 1 subunit 3 (T1R3) is a G protein-coupled receptor encoded by the TAS1R3 gene that can be specifically activated by certain sweeteners or umami agents for sweet/umami recognition. T1R3 is a potential target for regulating male reproduction. However, studies on the impact of non-nutritive sweeteners on reproduction are limited. In the present study, we evaluated the impact of the non-nutritive sweeteners (saccharin sodium, sucralose and acesulfame-K) on testosterone synthesis in testicular Leydig cells of Xiang pigs by comparing the relative abundance of mRNA transcripts and protein expression of T1R3, steroidogenic related factors, and intracellular cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), as well as testosterone levels using Western blotting, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). To clarify the specific mechanism, a dual luciferase assay was used to uncover the relationship between the transcription factors and steroidogenic enzyme. The acute intratesticular injection of a typical non-nutritive sweeteners was conducted to verify this impact in mouse. The results showed that saccharin sodium not only enhanced T1R3 expression in Leydig cells of Xiang pigs, but also caused significant increases in testosterone, cAMP, PKA, phosphorylation of specificity protein 1 (p-SP1), total protein of specificity protein 1 (SP1), steroidogenic acute regulatory protein (StAR), and 3β-hydroxysteroid dehydrogenase type 1 (3β-HSD1) (P<0.05). Similarly, treatment of Leydig cells with sucralose and acesulfame-K also increased testosterone level, protein expression of T1R3, 17-α-hydroxylase/17, 20-lyase (CYP17A1), and 3β-HSD1 (P<0.05). Treatment with SQ22536 (an adenylate cyclas inhibitor) or H89 (a PKA inhibitor) significantly reduced saccharin sodium-induced protein levels of p-SP1, StAR, CYP17A1, and 3β-HSD1 (P<0.05). In addition, a dual luciferase assay further demonstrated that SP1 significantly increased the promoter activity of CYP17A1 (P<0.05). When mouse testes were injected with saccharin sodium, T1R3, p-SP1, CYP17A1, and 3β-HSD1 were upregulated, leading to a significant testicular increase in testosterone and cAMP levels (P<0.05). These results suggest a mechanism by which the taste receptor T1R3 regulates testosterone production, and this mechanism may be linked to the cAMP-PKA pathway. Understanding the interrelationship between T1R3 and the cAMP-PKA-SP1 pathway contributes to clarify the regulatory mechanisms of male reproduction.

Exploring the Role of the TAS2R16 Protein and Its Single Nucleotide Variants in Pituitary Adenoma Development.

Pituitary adenoma (PA) is a common benign tumor that develops in the pituitary gland, causing hormonal imbalances and potential health issues. The TAS2R16 gene codes for a taste receptor and is involved in bitter taste perception, but there is currently no known direct link between this gene and pituitary adenoma. This study included 221 healthy controls and 131 patients with pituitary adenoma (PA) from the Lithuanian population. DNA was isolated from peripheral venous blood using the salt precipitation method. Genotyping was performed via RT-PCR. Statistical analysis was conducted with IBM SPSS Statistics 29.0 software, incorporating the Bonferroni correction for multiple comparisons. This study found that the TAS2R16 rs978739 C allele is less common in the non-invasive PA group compared to the control group (p = 0.045). The TAS2R16 rs860170 CT genotype reduces the likelihood of developing non-invasive PA by 1.9-fold under the codominant (p = 0.024) and overdominant (p = 0.030) models. The odds of developing non-invasive PA are reduced by 2-fold under the dominant (p = 0.021) model for TAS2R16 rs860170 CT + CC genotypes and by 2-fold under the additive (p = 0.018) model for each TAS2R16 rs860170 C allele. The PA group had higher serum levels of TAS2R16 than the control group (p < 0.001). The present study found that patients with the TAS2R16 rs978739 TT or CT genotype had higher serum TAS2R16 levels and protein concentrations than healthy individuals (p = 0.025 and p = 0.019, respectively), and those with the AA or AG genotype of TAS2R16 rs1357949 had higher protein concentrations (p = 0.005 and p = 0.007, respectively). The TAS2R16 rs978739 C allele was less common in the non-invasive PA group compared to the control group, while the TAS2R16 rs860170 CT genotype was linked to a reduced likelihood of developing non-invasive PA. Additionally, the PA group showed higher serum levels of TAS2R16, and increased serum protein concentrations were observed in PA patients with specific TAS2R16 variants.

Assessment of Correlation between Genetic Taste Perception Hormonal Fingerprint and Dental Caries Incidence in Schoolgoing Children: An In Vivo Study.

Genetic predilection toward sweeter cariogenic foods mediated by the TAS2R38 gene, tested by phenylthiourea [phenylthiocarbamide (PTC)] compounds. Some individuals find it extremely bitter whereas some find it completely tasteless, being classified as a taster and a nontaster respectively. A majority of nontasters prefer foods with sweeter and stronger flavors, thus making them more susceptible to dental caries. Genetic taste perception is greatly influenced by prenatal androgen exposure represented by hormonal fingerprint, that is, ratio of second to fourth digit lengths (2D:4D ratio), thus making it a precise biomarker to quantify an individual's genetic taste perception and in turn their caries susceptibility. To find a correlation of genetic taste perception with the hormonal fingerprint and dental caries prevalence in children. A total of 96 children were selected at random for the study and divided into two groups based on their gender. A genetic taste perception test was carried out using PTC strips, and they were classified as tasters and nontasters. Then, the hormonal fingerprint was recorded by calculating the ratio of the index finger and ring finger. Following this, decayed, missing, and filled teeth index (DMFT) was recorded. A strong positive correlation was observed among nontasters, with a preference for sweeter foods associated with a high caries index. Conversely, no relationship was found between genetic taste perception and the hormonal fingerprint. The present study positively demonstrates an association of genetic taste perception and dental caries due to an increased preference for sweeter foods among nontasters. Although no correlation was found between the genetic taste perception, the hormonal fingerprint, and the dental caries status of an individual. Kulshrestha A, Shah P, Jagtap C, et al. Assessment of Correlation between Genetic Taste Perception Hormonal Fingerprint and Dental Caries Incidence in Schoolgoing Children: An In Vivo Study. Int J Clin Pediatr Dent 2024;17(6):690-694.

Association of the bitter taste genes TAS2R38 and CA6 and breast cancer risk; a case-control study of Polish women in Poland and Polish immigrants in USA.

It is known that the perception of bitterness is mediated by type 2 bitter taste receptors (TAS2Rs). However, recent reports have suggested that the carbonic anhydrase 6 (CA6) gene may also influence bitterness sensing. Genetic variants in these genes could influence dietary intake of brassica vegetables, whose increased consumption has been observed in the literature, though inconsistently, to decrease breast cancer (BC) risk. We hypothesized that the estimated odds ratios (ORs) for the association between BC and taster diplotype (PAV/PAV) and/or genotype A/A, will be in the direction of increased BC risk, potentially due to reduced consumption of brassica vegetables. Using a case-control study of BC in Polish women in Poland (210 cases and 262 controls) and Polish immigrant women to USA (78 cases and 170 controls) we evaluated the association of the taster diplotypes in TAS2R38 gene and genotypes in the CA6 gene and BC risk in these two populations individually and jointly. No significant increase in risk was observed for the TAS2R38 PAV/PAV diplotype (tasters) in each population individually or in the joint population. For the CA6 gene, in the joint population, we observed an increased BC risk for the combined G/A and G/G genotypes (non-tasters) vs A/A (tasters), OR = 1.41 (95% CI 1.04-1.90, p = 0.026) which after adjustment for False Discovery Rate (FDR), was not significant at p≤0.05 level. However, for the joint population and for the combined genotype of the two genes AVI/AVI+G* (non-tasters) vs. PAV/*+A/A (tasters), we observed a significant increase in BC risk, OR = 1.77 (95%CI 1.47-2.74, p = 0.01), for the non-tasters, which remained significant after FDR adjustment. In conclusion for the joint population and the joint effect for the two bitter sensing genes, we observed an increase in BC risk for the bitterness non-tasters, association which is in the opposite direction to our original hypothesis.

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.

Investigating the Potential Influence of TAS2R16 Genetic Variants and Protein Levels on Multiple Sclerosis Development.

The study aimed to investigate the association between the TAS2R16 gene (rs860170, rs978739, rs1357949), TAS2R16 serum levels, and multiple sclerosis (MS). A total of 265 healthy control subjects and 218 MS patients were included in the study. Single nucleotide polymorphisms (SNPs) were tested by real-time polymerase chain reaction (RT-PCR). The serum concentration of TAS2R16 was measured using the ELISA method. Analyses revealed that the TAS2R16 rs860170 TT genotype was statistically significantly less frequent in the MS group than in the control group (p = 0.041), and the CC genotype was statistically significantly more frequent in the MS group than in the control group (p < 0.001). In the most robust (codominant) model, the CC genotype was found to increase the odds of MS by ~27-fold (p = 0.002), and each C allele increased the odds of MS by 1.8-fold (p < 0.001). Haplotype analysis of the rs860170, rs978739, and rs1357949 polymorphisms showed that the C-C-A haplotype was associated with a ~12-fold increased odds of MS occurrence (p = 0.02). Serum TAS2R16 levels were elevated in the MS group compared to control subjects (p = 0.014). Conclusions: The rs860170, rs978739, and rs1357949 polymorphisms demonstrated that the C-C-A haplotype and elevated TAS2R16 serum levels can promote the development of MS. These preliminary findings underscore the importance of specific genetic variants, such as rs860170, rs978739, and rs1357949, in MS risk. Additionally, elevated TAS2R16 serum levels in MS patients suggest a potential role in MS pathogenesis. These findings provide insights into the genetic and molecular mechanisms underlying MS and pave the way for personalized diagnostic and therapeutic strategies. Integrating genetic and serum biomarker data in MS research offers promising avenues for improving clinical outcomes and advancing precision medicine approaches in the future.

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.

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 of TAS1R2 (rs35874116 or rs9701796) Gene Polymorphism with Dental Caries: A Systematic Review and Meta-analysis

Background: Gene variations affecting taste preference and glucose consumption have recently been linked to dental caries. Aims: Possible associations between dental caries and the TAS1R2 gene polymorphisms rs35874116 and rs9701796 have been investigated, but conflicting results have been found. Therefore, a meta-analysis was conducted to find comprehensive and more specific results in this direction. Methods: The work started by searching English articles until April 2023 from the reliable databanks PubMed, Embase, Scopus and Web of Science. Then, relevant articles were carefully chosen in various steps based on defined selection criteria and assessed by comprehensive meta-analysis v.2.0 software. Results: Based on six selected articles, the meta-analyses showed a significant association between dental caries risk and the TAS1R2 gene polymorphism rs9701796 (p&lt;0.05), with the GG genotype in rs9701796 increasing the risk. No significant relation was found for rs35874116. Conclusion: This meta-analysis concluded that the rs9701796 polymorphism increases the risk of dental caries. Studies with larger sample sizes can clarify the relationship further.

Genetic variation in TAS2R38 bitterness receptor is associated with body composition in Korean females

Bitterness-receptor gene TAS2R38 is associated with taste sensitivity and dietary behaviour, and is known to play a critical role in adiposity. However, evidence regarding body composition from a large cohort is lacking. This study aimed to ascertain whether TAS2R38 rs10246939 C > T bitterness genetic variation is associated with body composition in Korean individuals. The TAS2R38 rs10246939 genotypes, anthropometric measurements, and body composition of 1,843 males and 1,801 females from the Korean Genome and Epidemiology Study were analysed. Findings suggested that there was a significant difference in body fat components by TAS2R38 genotype. Furthermore, the bitterness genotype exhibited a positive association with adiposity markers in females. The TT genotype showed greater body mass index, body fat percentage, and degree of obesity than those with the C allele. However, such an association was not observed in males. In conclusion, this study suggests that TAS2R38 rs10246939 is associated with fat tissue markers in Korean females.

A vertebrate-wide catalogue of T1R receptors reveals diversity in taste perception

Taste is a vital chemical sense for feeding behaviour. In mammals, the umami and sweet taste receptors comprise three members of the taste receptor type 1 (T1R/TAS1R) family: T1R1, T1R2 and T1R3. Because their functional homologues exist in teleosts, only three TAS1R genes generated by gene duplication are believed to have been inherited from the common ancestor of bony vertebrates. Here, we report five previously uncharacterized TAS1R members in vertebrates, TAS1R4, TAS1R5, TAS1R6, TAS1R7 and TAS1R8, based on genome-wide survey of diverse taxa. We show that mammalian and teleost fish TAS1R2 and TAS1R3 genes are paralogues. Our phylogenetic analysis suggests that the bony vertebrate ancestor had nine TAS1Rs resulting from multiple gene duplications. Some TAS1Rs were lost independently in descendent lineages resulting in retention of only three TAS1Rs in mammals and teleosts. Combining functional assays and expression analysis of non-teleost fishes we show that the novel T1Rs form heterodimers in taste-receptor cells and recognize a broad range of ligands such as essential amino acids, including branched-chain amino acids, which have not been previously considered as T1R ligands. This study reveals diversity of taste sensations in both modern vertebrates and their ancestors, which might have enabled vertebrates to adapt to diverse habitats on Earth.

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.

Altered expression levels of TAS1R2 and TAS1R3 genes among SARS-CoV-2 variants of concerns.

The most common symptoms of coronavirus infections are fever, cough, shortness of breath, headache, ache of joints, a loss of smell and loss of taste, and etc. Early studies suggested that smell and taste receptors were associated with pathogenic detection and immunity. Thus, we aimed to evaluate the expression profile of gene receptors that are related to taste, smell, and appetite control in COVID-19 patients and their putative correlation with SARS-CoV-19 variants. Gene expression levels of TAS1R2, TAS1R3, TAS2R38, OR51E1, LEPR, GHRL were analyzed in 100 COVID-19 patients and 100 SARS-CoV-2 RT-qPCR negative group. The expression levels of TAS1R2 and TAS1R3 genes were significantly decreased in COVID-19 patients who were infected with Delta variant. However, the TAS2R38 gene expression level was significantly lower when compared to the control group. The TAS1R2 gene expression was positively correlated with TAS1R3, and TAS2R38 genes (p = 0.001, p = 0.025, respectively). TAS1R2, TAS1R3, and TAS2R38 gene expression levels were decreased in the Delta variant compared to the Omicron BA.1 variant in the studied groups. These results provided a significant clue for the temporary taste loss, especially in patients infected with the Delta variant, which is the most disruptive and symptomatic variant causing hospitalizations, and deaths compared to other variants may be because ACE2 is expressed in the taste buds and high replication of SARS-CoV-2 in the infected gustatory cells in the taste bud generates inflammation and then could eventually destroy the cells. This gustatory cell damage may cause malfunction of the gustatory system.

Hipofizės adenoma: literatūros apžvalga ir sąsajos su TAS2R16 (rs978739, rs1357949) geno polimorfizmais

The pituitary gland is the primary regulatory gland in the endocrine system transmitting signals from the hypothalamus to target organs through hormone release. Through the release of hormones, the pituitary gland regulates vital physiological functions: growth, reproduction, metabolism, and the stress response. Disorders in the pituitary gland can cause damage, such as pituitary adenomas (PA). PA is the most common benign tumor arising from epithelial cells of the anterior pituitary gland. PA is one of the most common tumors of the central nervous system. PA is differentiated by hormone secretion into non-secretory (non- functional) and secretory (functionally active). Excess hormones secreted by PA can cause clinical syndromes, such as hyperprolactinemia (caused by excessive secretion of prolactin), acromegaly (due to excess growth hormone), and Cushing’s syndrome (due to excessive production of the adrenocorticotropic hormone ACTH)). Studies show that the prevalence of adenomas in the population is approximately 80/100,000. The occurrence of PA is influenced not only by somatic or germ cell defects but also by environmental factors. The exact cause of PA is still unclear, but it is known that a small part (~5%) of PA due to hereditary syndromes is caused by gene changes. Considering the influence of environmental factors and genetic alterations that affect the occurrence of PA, new genetic markers can be searched to detect this disease. One of the risk factors contributing to the development of PA and its aggressiveness is alcohol consumption. Excessive alcohol consumption affects not only the development of PA but also the manifestation of other cancers. A recent study has investigated the association of TAS2R16 gene single nucleotide polymorphisms (SNPs) with colon cancer, as SNPs in this gene have been found to increase alcohol dependence. Based on the association of TAS2R16 SNPs with cancer, we decided to investigate the association of TAS2R16 gene (rs978739, rs1357949) polymorphisms with PA.

TAS2R38 bitter taste perception in the Koṅkaṇī Sārasvata Brahmin population.

The TAS2R38 gene carries markers for phenylthiocarbamide (PTC) sensitivity. Various studies have investigated the genotype-phenotype association pattern for bitter tasting ability and other factors in different populations. However, a paucity of such information for endogamous Indian populations is the reason behind this study. To study the association of phenylthiocarbamide (PTC) sensitivity with TAS2R38 gene variations in Koṅkaṇī Sārasvata Brahmin population. We studied the association of the alleles rs714598, rs1726866, rs10246939 with PTC sensitivity and other factors in the Koṅkaṇī Sārasvata Brahmin population. DNA was extracted from 114 individuals belonging to the Koṅkaṇī Sārasvata Brahmin community. The TAS2R38 gene was sequenced to find the genotype distribution pattern. The association between genotype and phenotype was checked using the Chi-Square test and multifactorial logistical regression. We observed a 58.8% frequency of the AVI haplotype, which is the most prevalent in European populations. A higher number of non-taster haplotypes and diplotypes were observed in Koṅkaṇī Sārasvata Brahmins, with the allele rs10246939 showing a significant association with PTC bitter taste sensitivity in both allelic (p = 8.6 × 10-4; Allele-G, OR = 3.57 [95% CI = 1.66-7.69]) and genotype-based (p = 6.9 × 10-4; genotype-AG, OR = 3.11 [95% CI = 0.73-13.20]; genotype-GG, OR = 40 [95% CI = 3.58-447.03]) tests. Our results are in line with earlier studies, which report an association between PTC sensitivity and the TAS2R38 gene in different populations. In the global context, Koṅkaṇī Sārasvata Brahmins, who are mostly distributed along the southwestern coast of India, show a PTC sensitivity pattern slightly similar to that of West Eurasian populations. Our findings suggest ancestry specific selection in TAS2R38 gene variations for taste sensitivity at global level.

VARIATIONS IN THE PERCEPTION OF BITTER TASTE MAY MODULATE THE RISK OF HYPERTENSION

Objective: The perception of bitter taste conditioned by the TAS2R38 gene (combined Proline/Alanine/Valine and Isoleucine phenotypes) may be associated with food consumption. Individuals with one copy of PAV are bitter tasters, with two copies of AVI are non-bitter tasters, and with AAV &lt; AAI &lt; PAI are intermediate bitter tasters. Consumption salt balance is determined by the function of the epithelial sodium channels that lead to its preference and the bitter taste receptors associated with its aversion. In turn, a chronic high salt intake was associated with the inhibition of bitter receptors with less salty taste aversion leading to potential higher consumption and risk of hypertension. The objective was to evaluate the influence of bitter taste perception on the risk of arterial hypertension. Design and method: DNA from 339 individuals was quantified and genotyped by reverse transcription followed by polymerase chain reaction (RT-PCR). Blood pressure was determined by standard methods. Arterial hypertension was diagnosed in 141 individuals who were compared with 198 normotensive individuals. Thyroid functional status is determined by clinical history, physical examination, FT4, FT3, TSH, antiperoxidase, antithyroglobulin, and TRAB antibodies. Hypothyroidism at 33.3%, hyperthyroidism 14.3% and euthyroidism 52.35%. Statistics: chi2 and t-Student, considering significance &lt;0.05. Results: The frequencies of the TAS2R38 diplotypes were: PVI/PVI (26%); PVV/PVI (0.9%); PVV/AVI(10.6%); PVV/AVV(0.9%); AVV/AVV(2.4%); PAI/PVI(0.3%); PAV/PVI(5.95%); PAV/AVI(37.5%); AAV/AAV(12.7%); PAV/AAV(2.75%) and PAV/AAI(0.3%). The TAS2R38 AAV/AAV and PAV/AAV diplotypes showed a lower risk of hypertension adjusted for thyroid dysfunction, compared to the remaining diplotypes of this gene, with OR = 0.458[0.236-0.887], p = 0.021. Other diplotypes showed no significant association. Conclusions: Individuals with bitter tasting associated with AAV genotypes may be less likely to develop hypertension compared to other bitter tasters. The lower risk of hypertension in these genotypes may be associated with greater functionality of bitter taste receptors associated with aversion to salt intake. In conclusion, the genetic polymorphisms of the bitter taste gene may influence the risk for arterial hypertension and may therefore be considered potential future therapeutic targets. The absence of bitter-insensitive individuals (AVI/AVI) in this sample limits the understanding of the influence of these genotypes on the risk of hypertension.

Genetic Preference for Sweet Taste in Mothers Associates with Mother-Child Preference and Intake.

Taste perception is a well-documented driving force in food selection, with variations in, e.g., taste receptor encoding and glucose transporter genes conferring differences in taste sensitivity and food intake. We explored the impact of maternal innate driving forces on sweet taste preference and intake and assessed whether their children differed in their intake of sweet foods or traits related to sweet intake. A total of 133 single nucleotide polymorphisms (SNPs) in genes reported to associate with eating preferences were sequenced from saliva-DNA from 187 mother-and-child pairs. Preference and intake of sweet-, bitter-, sour-, and umami-tasting foods were estimated from questionnaires. A total of 32 SNP variants associated with a preference for sweet taste or intake at a p-value < 0.05 in additive, dominant major, or dominant minor allele models, with two passing corrections for multiple testing (q < 0.05). These were rs7513755 in the TAS1R2 gene and rs34162196 in the OR10G3 gene. Having the T allele of rs34162196 was associated with higher sweet intake in mothers and their children, along with a higher BMI in mothers. Having the G allele of rs7513755 was associated with a higher preference for sweets in the mothers. The rs34162196 might be a candidate for a genetic score for sweet intake to complement self-reported intakes.

Influence of the TAS2R38 Gene Single Nucleotide Polymorphisms in Metabolism and Anthropometry in Thyroid Dysfunction.

The gene TAS2R38 single nucleotide polymorphisms (SNPs-P49A, A262V and V296I) can condition bitter tasting by PAV (proline-alanine-valine) and non-bitter-tasting by AVI (alanine-valine-isoleucine) homozygosity. We evaluated this polymorphisms association with thyroid function, metabolism and anthropometry parameters determined by: Endpoint analysis (SNPs); DXA (fat mass-%, total fat mass-kg, lean mass-kg); Standard methods (lipid metabolism parameters, HbA1c-%, glycemia-mg/dL, insulinemia-µIU/mL, HOMA-IR, uricemia-mg/dL, calcemia-mg/dL and BMI-kg/m2); ELISA (leptinemia-ng/mL); Spectrophotometry (Angiotensin Converting Enzyme activity-UI/L). Statistics: SPSS program; OR [IC95%]; p < 0.05. Sample: 114 hypothyroid, 49 hyperthyroid, and 179 controls. An association between A262V-valine-valine and hypothyroidism/hyperthyroidism was verified (OR = 2.841; IC95% [1.726-4.676]), p < 0.001/OR = 8.915; IC95% [4.286-18.543]), p < 0.001). Protector effect from thyroid dysfunction: A262V-alanine-valine (OR = 0.467; IC95% [0.289-0.757], p = 0.002/OR = 0.132; IC95% [0.056-0.309], p < 0.001) and PAV (OR = 0.456; IC95% [0.282-0.737], p = 0.001/OR = 0.101; IC95% [0.041-0.250], p < 0.001). Higher parameter values associated with genotypes were: fat-mass-% (V296I-valine-isoleucine), lean-mass (P49A-proline-proline; PVI), leptin (AVI), HbA1c (A262V-alanine-valine) and lower values in lean-Mass (AVI; PVV), leptin (A262V-alanine-alanine), HbA1c (PVV), uricemia (V296I-valine-isoleucine), glycemia (A262V-alanine-alanine; AAV) and plasma triglycerides (PVV). In conclusion, TAS2R38 influences thyroid function, body composition and metabolism. Bitter taste perception (PAV) and the genotype A262V-alanine-valine can protect from thyroid dysfunction. AVV, PVV and genotype A262V-valine-valine may confer higher predisposition for thyroid dysfunction, particularly PVV for hyperthyroidism.