Genetic, functional, and phenotypic diversity in TAS2R38-mediated bitter taste perception

Maik Behrens, Howard C. Gunn, Purita C M Ramos, Wolfgang Meyerhof, Stephen P. Wooding

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Mutational polymorphism in the TAS2R38 bitter taste receptor is a key determinant of threshold taste detection of isolated compounds, such as phenylthiocarbamide (PTC) and propylthiouracil (PROP), as well as complex orosensation-mediated traits such as diet choice and smoking habits. These relationships are accounted for, in part, by 2 common alleles differing in functionality, TAS2R38-PAV and TAS2R38-AVI. However, TAS2R38 harbors extensive additional polymorphism whose functional significance remains unknown. To examine this variation, we ascertained genetic diversity in 56 Caucasian subjects via whole-gene sequencing, analyzed allele-specific responses to 5 TAS2R38 agonists (PTC, PROP, goitrin, methimazole, and sinigrin) using in vitro assays, and assessed genotypic associations with threshold detection phenotypes. Sequencing identified 3 single-nucleotide substitutions encoding 3 amino acid changes (C145G/P49A, C785T/A262V, and A886G/I296V), which combined to form 6 haplotypes in our sample. In vitro assays revealed a continuous range of response across alleles, and associations with threshold were significant for all single nucleotide polymorphisms (P < 0.002) and PAV/AVI haplotypes (P < 0.001). Haplotypes other than PAV and AVI did not exhibit phenotypic associations in our sample, possibly as a result of their low frequencies. However, prior studies have indicated that these alleles are common in some global regions, suggesting that alleles rare in our sample may be phenotypically relevant in other populations.

Original languageEnglish (US)
Pages (from-to)475-484
Number of pages10
JournalChemical Senses
Volume38
Issue number6
DOIs
StatePublished - Jul 2013

Keywords

  • Bitter
  • Goitrogen
  • Isothiocyanate
  • Phenylthiocarbamide
  • TAS2R
  • Taste

ASJC Scopus subject areas

  • Physiology
  • Sensory Systems
  • Physiology (medical)
  • Behavioral Neuroscience

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  • Cite this

    Behrens, M., Gunn, H. C., Ramos, P. C. M., Meyerhof, W., & Wooding, S. P. (2013). Genetic, functional, and phenotypic diversity in TAS2R38-mediated bitter taste perception. Chemical Senses, 38(6), 475-484. https://doi.org/10.1093/chemse/bjt016