title: The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception.
abstract: Individual differences in perception are ubiquitous within the chemical senses: taste, smell, and chemical somesthesis . A hypothesis of this fact states that polymorphisms in human sensory receptor genes could alter perception by coding for functionally distinct receptor types . We have previously reported evidence that sequence variants in a presumptive bitter receptor gene (hTAS2R38) correlate with differences in bitterness recognition of phenylthiocarbamide (PTC) . Here, we map individual psychogenomic pathways for bitter taste by testing people with a variety of psychophysical tasks and linking their individual perceptions of the compounds PTC and propylthiouracil (PROP) to the in vitro responses of their TAS2R38 receptor variants. Functional expression studies demonstrate that five different haplotypes from the hTAS2R38 gene code for operatively distinct receptors. The responses of the three haplotypes we also tested in vivo correlate strongly with individuals' psychophysical bitter sensitivities to a family of compounds. These data provide a direct molecular link between heritable variability in bitter taste perception to functional variations of a single G protein coupled receptor that responds to compounds such as PTC and PROP that contain the N-C=S moiety. The molecular mechanisms of perceived bitterness variability have therapeutic implications, such as helping patients to consume beneficial bitter-tasting compounds-for example, pharmaceuticals and selected phytochemicals.
authors.affiliation: German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Bufe
authors.forename: Paul A S
authors.initials: PA
authors.lastname: Breslin
authors.forename: Christina
authors.initials: C
authors.lastname: Kuhn
authors.forename: Danielle R
authors.initials: DR
authors.lastname: Reed
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Tharp
authors.forename: Jay P
authors.initials: JP
authors.lastname: Slack
authors.forename: Un-Kyung
authors.initials: UK
authors.lastname: Kim
authors.forename: Dennis
authors.initials: D
authors.lastname: Drayna
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meyerhof
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016018:Least-Squares Analysis; D010670:Phenylthiourea; D011441:Propylthiouracil; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D013649:Taste / Q000502:physiology*; D000098706:Taste Receptors, Type 2
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D010670:Phenylthiourea; D011441:Propylthiouracil
references.citation: Cell. 2000 Mar 17;100(6):703-11
references.pmid: 10761935
references.citation: Nat Genet. 2002 Nov;32(3):397-401
references.pmid: 12379855
references.citation: Am J Hum Genet. 2004 Apr;74(4):637-46
references.pmid: 14997422
references.citation: Ann Eugen. 1951 Sep;16(2):119-28
references.pmid: 14885872
references.citation: Chem Senses. 2004 Sep;29(7):583-93
references.pmid: 15337684
references.citation: Science. 1979 Aug 31;205(4409):934-5
references.pmid: 472717
references.citation: Nutr Rev. 2001 Jun;59(6):163-9
references.pmid: 11444592
references.citation: Percept Psychophys. 2001 Jul;63(5):761-76
references.pmid: 11521845
references.citation: Alcohol Clin Exp Res. 2004 Nov;28(11):1629-37
references.pmid: 15547448
references.citation: Nat Genet. 2003 Jun;34(2):143-4
references.pmid: 12730696
references.citation: Ann Eugen. 1949 Oct;15(1):32-45
references.pmid: 15409616
references.citation: Biochem Biophys Res Commun. 2001 Jul 6;285(1):147-51
references.pmid: 11437385
references.citation: Ann Hum Biol. 2001 Mar-Apr;28(2):111-42
references.pmid: 11293722
references.citation: Mol Biol Evol. 2005 Mar;22(3):432-6
references.pmid: 15496549
references.citation: Science. 2003 Feb 21;299(5610):1221-5
references.pmid: 12595690
references.citation: J Neurosci. 2004 Nov 10;24(45):10260-5
references.pmid: 15537898
references.citation: Proc Natl Acad Sci U S A. 1932 Jan;18(1):120-30
references.pmid: 16577422
references.citation: J Neurosci. 2004 Mar 3;24(9):2296-303
references.pmid: 14999080