The UGT2A1/UGT2A2 locus is associated with COVID-19-related loss of smell or taste.

Using online surveys, we collected data regarding COVID-19-related loss of smell or taste from 69,841 individuals. We performed a multi-ancestry genome-wide association study and identified a genome-wide significant locus in the vicinity of the UGT2A1 and UGT2A2 genes. Both genes are expressed in the olfactory epithelium and play a role in metabolizing odorants. These findings provide a genetic link to the biological mechanisms underlying COVID-19-related loss of smell or taste.

Loss of sweet taste despite the conservation of sweet receptor genes in insectivorous bats.

The evolution of taste perception is usually associated with the ecology and dietary changes of organisms. However, the association between feeding ecology and taste receptor evolution is unclear in some lineages of vertebrate animals. One example is the sweet taste receptor gene Tas1r2 Previous analysis of partial sequences has revealed that Tas1r2 has undergone equally strong purifying selection between insectivorous and frugivorous bats. To test whether the sweet taste function is also important in bats with contrasting diets, we examined the complete coding sequences of both sweet taste receptor genes (Tas1r2 and Tas1r3) in 34 representative bat species. Although these two genes are highly conserved between frugivorous and insectivorous bats at the sequence level, our behavioral experiments revealed that an insectivorous bat (Myotis ricketti) showed no preference for natural sugars, whereas the frugivorous species (Rousettus leschenaultii) showed strong preferences for sucrose and fructose. Furthermore, while both sweet taste receptor genes are expressed in the taste tissue of insectivorous and frugivorous bats, our cell-based assays revealed striking functional divergence: the sweet taste receptors of frugivorous bats are able to respond to natural sugars whereas those of insectivorous bats are not, which is consistent with the behavioral preference tests, suggesting that functional evolution of sweet taste receptors is closely related to diet. This comprehensive study suggests that using sequence conservation alone could be misleading in inferring protein and physiological function and highlights the power of combining behavioral experiments, expression analysis, and functional assays in molecular evolutionary studies.

Genetic taste blindness to bitter and body composition in childhood: a Mendelian randomization design.

BACKGROUND: The ability to taste 6-n-propylthiouracil (PROP) may be associated with body composition, but previous findings from observational studies are conflicting and cannot be interpreted causally. The aim of this study was to estimate the causal association between PROP taster status and body composition in a population-based cohort study. METHODS: The study was embedded in a population-based prospective birth cohort study. The TAS2R38 genotype (rs713598) was used as an instrumental variable (IV) to obtain unbiased effect estimates of the relation between PROP taster status and body weight (n=3778). Adiposity measures included body mass index (BMI) and fat mass measured by dual- energy X-ray absorptiometry scan at the child's age of 6 years. Associations were investigated using both ordinary linear regression (OLS) and two-stage least squares regression (2SLS). RESULTS: Non-taster girls had higher BMI standard deviation scores (SDS) and higher body fat as compared with taster girls (results from linear regression BMI SDS: -0.09, P=0.023, body fat mass (%): -0.49, P=0.028). The TAS2R38 genotype predicted PROP phenotype (F=240), indicating a strong IV. The 2SLS effect estimates were imprecise but similar to the observational estimates (-0.08 for BMI SDS and -0.46 for body fat mass %) and were not significantly different from the OLS results (Hausman test: P>0.10). For boys there were no differences observed between tasters and non-tasters. CONCLUSIONS: Our findings suggest a causal relation between PROP taster status and body weight among 6-year-old girls; Mendelian randomization was consistent with conventional estimates. In contrast, body weight among boys appeared to be independent of the PROP taster status. Further research should focus on possible underlying pathways, such as dietary behavior.

Patients with hypogeusia show changes in expression of T2R taste receptor genes in their tongues.

OBJECTIVES/HYPOTHESIS: Taste receptor genes associated with bitterness belong to the T2R gene family. In this study, we compared the expression of genes of the T2R family in the tongues of patients with hypogeusia to those in healthy subjects and examined the possibility that T2R genes are involved in the pathogenesis of hypogeusia. STUDY DESIGN: Prospective clinical and basic study. METHODS: The control group consisted of 24 healthy people. The patient group consisted of 40 subjects with hypogeusia who were confirmed to have abnormally elevated taste thresholds including that of bitter taste. A tissue sample was collected from each individual by scraping the mucosa on the foliate papillae of the tongue. Total RNA was extracted from each sample and reverse transcribed. The expression of 10 T2R genes (TAS2R40, -R42, -R43, and -R48, and T2R3, -R8, -R9, -R10, -R13, and -R16) was evaluated by reverse transcriptase-polymerase chain reaction. RESULTS: Comparison of the frequency of gene expression between the control group and patients with hypogeusia showed that the frequency of expression of six receptor genes were significantly reduced in the hypogeusia patients. In particular, TAS2R40 showed a significant and marked decrease in the frequency of expression regardless of the cause or severity of hypogeusia. CONCLUSIONS: Our results suggest that decreased expression of taste-associated genes may be involved in hypogeusia in humans. In addition, the evaluation of taste receptor gene expression may be useful clinically for an objective diagnosis of hypogeusia or to evaluate the severity of the disorder.

Construction of a taste-blind medaka fish and quantitative assay of its preference-aversion behavior.

In vertebrates, the taste system provides information used in the regulation of food ingestion. In mammals, each cell group within the taste buds expresses either the T1R or the T2R taste receptor for preference-aversion discrimination. However, no such information is available regarding fish. We developed a novel system for quantitatively assaying taste preference-aversion in medaka fish. In this study, we prepared fluorescently labeled foods with fine cavities designed to retain tastants until they were bitten by the fish. The subjects were fed food containing a mixture of amino acids and inosine monophosphate (AN food), denatonium benzoate (DN food) or no tastant (NT food), and the amounts of ingested food were measured by fluorescence microscopy. Statistical analysis of the fluorescence intensities yielded quantitative measurements of AN food preference and DN food aversion. We then generated a transgenic fish expressing dominant-negative Galpha(i2) both in T1R-expressing and in T2R-expressing cells. The feeding assay revealed that the transgenic fish was unable to show a preference for AN food and an aversion to DN food. The assay system was useful for evaluating taste-blind behaviors, and the results indicate that the two taste signaling pathways conveying preferable and aversive taste information are conserved in fish as well as in mammals.

Adiposity in middle-aged women is associated with genetic taste blindness to 6-n-propylthiouracil.

OBJECTIVE: Taste blindness to the bitterness of 6-n-propylthiouracil (PROP) may be a genetic marker for food preferences and dietary choices that ultimately influence body weight. A previous study in middle-aged women showed that those who were taste blind to PROP (i.e., nontasters) had higher BMIs than those with the greatest sensitivity to PROP (i.e., supertasters). This study tested the hypothesis that the nontaster phenotype was associated with greater adiposity in middle-aged women. RESEARCH METHODS AND PROCEDURES: Forty women with a mean BMI of 26.6+/-1.3 kg/m2 and a mean age of 41.8+/-1.8 years were recruited from the local community. They were classified as nontasters (n=8), medium tasters (n=18), or supertasters (n=14) of PROP using a filter paper screening procedure. Anthropometric measures included height, weight, body fatness, triceps skinfold thickness, and waist circumference. Dietary restraint and disinhibition were also measured to assess cognitions associated with body weight. RESULTS: BMI was 6.2 units higher in nontaster women compared with supertaster women (29.7+/-0.9 vs. 23.5+/-0.9, respectively; p<0.05). Body fatness (p<0.01) and triceps skinfold thickness (p<0.05) were also higher in these women. Waist circumference showed a trend in the appropriate direction. Although disinhibition was associated with greater adiposity, the relation between PROP status and adiposity was not altered after controlling for disinhibition. DISCUSSION: The PROP nontaster phenotype was strongly associated with several measures of adiposity in middle-aged women. These data confirm our previous findings and suggest that the PROP polymorphism may be a reliable indicator of weight gain susceptibility.