Please use this identifier to cite or link to this item: doi:10.22028/D291-42057
Title: Differential Activation of TAS2R4 May Recover Ability to Taste Propylthiouracil for Some TAS2R38 AVI Homozygotes
Author(s): Nolden, Alissa A.
Behrens, Maik
McGeary, John E.
Meyerhof, Wolfgang
Hayes, John E.
Language: English
Title: Nutrients
Volume: 16
Issue: 9
Publisher/Platform: MDPI
Year of Publication: 2024
Free key words: propylthiouracil
phenylthiocarbamide
individual differences
supertasting
suprathreshold
psychophysics
genetic variation
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: 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.
DOI of the first publication: 10.3390/nu16091357
URL of the first publication: https://doi.org/10.3390/nu16091357
Link to this record: urn:nbn:de:bsz:291--ds-420577
hdl:20.500.11880/37730
http://dx.doi.org/10.22028/D291-42057
ISSN: 2072-6643
Date of registration: 28-May-2024
Faculty: M - Medizinische Fakultät
Department: M - Physiologie
Professorship: M - Keiner Professur zugeordnet
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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