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

Risso, Davide; Mezzavilla, Massimo; Pagani, Luca; Robino, Antonietta; Morini, Gabriella; Tofanelli, Sergio; Carrai, Maura; Campa, Daniele; Barale, Roberto; Caradonna, Fabio; Gasparini, Paolo; Luiselli, Donata; Wooding, Stephen; Drayna, Dennis

doi:10.1038/srep25506

Cited by 78 publications

(68 citation statements)

References 52 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of the bitter receptors responsible for this response (T2R38, encoded by the TAS2R38 gene) also has a well-understood role in the taste system. This gene has two main genotypes, a taster and non-taster form, that are almost equally common in most human populations, with the majority of people being heterozygous [6–8]. Heterozygous people are able to perceive the bitterness of the ligand, albeit at a reduced intensity relative to people who are homozygous for the taster form [9].…”

mentioning

confidence: 99%

Tissue dependent expression of bitter receptorTAS2R38mRNA

Douglas

Lin

Mansfield

et al. 2018

Preprint

View full text Add to dashboard Cite

TAS2R38 is a human bitter receptor gene with a common but inactive allele and people homozygous for the inactive form cannot perceive certain bitter compounds. The frequency of the inactive and active form of this receptor is nearly equal in many human populations and heterozygotes (with one copy of the active form and another copy of the inactive form) have the most common diplotype. However, heterozygotes differ markedly in their perception of bitterness, in part perhaps because of differences in TAS2R38 mRNA expression. Other tissues including the nasal sinuses express this receptor, where it contributes to pathogen defense. We asked whether heterozygotes with high TAS2R38 mRNA expression in taste tissue were also likely to express more TAS2R38 mRNA in sinonasal tissue. To that end, we measured TAS2R38 bitter taste receptor mRNA by qPCR in biopsied tissue, and learned that expression amount of one is not related to the other. We confirmed the general independence of expression in other tissue expressing TAS2R38 mRNA using autopsy data from the GTEx project. Taste tissue TAS2R38 mRNA expression among heterozygotes is unlikely to predict expression in other tissues, perhaps reflecting tissue-dependent function and hence regulation of this protein.

show abstract

mentioning

confidence: 99%

Tissue dependent expression of bitter receptorTAS2R38mRNA

Douglas

Lin

Mansfield

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…Gene polymorphisms in bitter sensing TAS2R38 variants determine the sensitivity to bitter substance phenylthiocarbamide in humans (Sandell and Breslin, 2006;Risso et al, 2016) and have been associated with food preferences (Sandell and Breslin, 2006), alcohol intake (Duffy et al, 2004), obesity (Tepper et al, 2008) and susceptibility to respiratory pathogens (Lee et al, 2012). Similarly, other gene variants of TAS2R14 and TAS2R50 have been associated with human diseases such as cancer and cardiovascular disease, respectively (Campa et al, 2010;Akao et al, 2012).…”

Section: Bitter Sensingmentioning

confidence: 99%

Review: Chemosensing of nutrients and non-nutrients in the human and porcine gastrointestinal tract

Roura

Depoortere

Navarro

2019

Animal

View full text Add to dashboard Cite

The gastrointestinal tract (GIT) is an interface between the external and internal milieus that requires continuous monitoring for nutrients or pathogens and toxic chemicals. The study of the physiological/molecular mechanisms, mediating the responses to the monitoring of the GIT contents, has been referred to as chemosensory science. While most of the progress in this area of research has been obtained in laboratory rodents and humans, significant steps forward have also been reported in pigs. The objective of this review was to update the current knowledge on nutrient chemosensing in pigs in light of recent advances in humans and laboratory rodents. A second objective relates to informing the existence of nutrient sensors with their functionality, particularly linked to the gut peptides relevant to the onset/offset of appetite. Several cell types of the intestinal epithelium such as Paneth, goblet, tuft and enteroendocrine cells (EECs) contain subsets of chemosensory receptors also found on the tongue as part of the taste system. In particular, EECs show specific co-expression patterns between nutrient sensors and/or transceptors (transport proteins with sensing functions) and anorexigenic hormones such as cholecystokinin (CCK), peptide tyrosine tyrosine (PYY) or glucagon-like peptide-1 (GLP-1), amongst others. In addition, the administration of bitter compounds has an inhibitory effect on GIT motility and on appetite through GLP-1-, CCK-, ghrelin- and PYY-labelled EECs in the human small intestine and colon. Furthermore, the mammalian chemosensory system is the target of some bacterial metabolites. Recent studies on the human microbiome have discovered that commensal bacteria have developed strategies to stimulate chemosensory receptors and trigger host cellular functions. Finally, the study of gene polymorphisms related to nutrient sensors explains differences in food choices, food intake and appetite between individuals.

show abstract

“…The variants in TAS2R7 and TAS2R42 associated with tea intake are in moderate LD (R 2 =0.59, GBR). The variants in TAS2R38 that are associated with tea intake are in high LD and are known to affect the ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) ( Figure S4) (Kim, 2003;Risso et al, 2016). The ability to taste PTC follows a dominant model of inheritance where the alternate "taster" allele C is dominant to the "non-taster" reference T allele for rs10246939 (Kim, 2003).…”

Section: Genetic Variation In Orphan Gpcrs Associated With Quantitatimentioning

confidence: 99%

Medical relevance of common protein-altering variants in GPCR genes across 337,205 individuals in the UK Biobank

DeBoever

Venkatakrishnan

Paggi

et al. 2019

Preprint

View full text Add to dashboard Cite

G protein-coupled receptors (GPCRs) drive an array of important physiological functions and are the targets of nearly one-third of all FDA approved drugs. Large scale genomic initiatives are mapping the genetic diversity in GPCRs, however, a map of which GPCR genetic variants are associated with phenotypic variation and disease is lacking. Furthermore, the mechanistic basis of how the individual GPCR genetic variants regulate molecular function is also largely unknown. We performed a phenome-wide association analysis for 269 common protein-altering variants in 156 GPCRs and 275 phenotypes using data from 337,205 unrelated white British UK Biobank participants and identified 138 associations at a false discovery rate of 5%. We found a novel association between rs12295710 in MRGPRE, a member of the Mas-related receptor family involved in nociception, and migraine risk. We also identified an association between rs3732378, a missense mutation in the binding pocket of CX3CR1, and hypothyroidism. Five orphan GPCRs had eight genetic associations, highlighting novel biology for these receptors of unknown function. We found several associations between GPCR variants and food intake phenotypes, including an association between the variants in TAS2R38 known to affect the ability to taste phenylthiocarbamide and tea intake as well as a non-additive associations between variants in TAS2R19 and TAS2R31 and coffee and tea intake. Finally, we tested whether genetic variants in ADRB2 associated with immune cell amounts and pulmonary function affect downstream signaling pathways and found that two ADRB2 haplotypes are associated with differential signaling relative to the most common haplotype. Overall, this study provides a map of genetic associations for GPCR coding variants across a wide variety of phenotypes that can inform future drug discovery efforts targeting GPCRs.

show abstract

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

Cited by 78 publications

References 52 publications

Tissue dependent expression of bitter receptorTAS2R38mRNA

Tissue dependent expression of bitter receptorTAS2R38mRNA

Review: Chemosensing of nutrients and non-nutrients in the human and porcine gastrointestinal tract

Medical relevance of common protein-altering variants in GPCR genes across 337,205 individuals in the UK Biobank

Contact Info

Product

Resources

About