One Gene, Three Answers: What TAS2R38 Decides

Put a strip of paper treated with a compound called PTC on your tongue. Some people recoil from it. Others taste nothing at all and assume the whole thing is a trick.

Both are telling the truth. The difference is one receptor gene, TAS2R38, and it is one of the clearest demonstrations in human genetics that two people can live in measurably different sensory worlds.

That much has been known since the 1930s. What we finished publishing this week is the part that comes after: the same three coding changes turn up in two more places that have nothing obvious to do with vegetables.

One: what food tastes like

Three changes in TAS2R38 travel together and are read as one unit. PAV builds a receptor that responds strongly — the taster form. AVI builds one that barely responds. Which pair you inherit decides whether PTC, PROP, and the glucosinolates that give broccoli, brussels sprouts, kale and turnip their bite register as sharply bitter or as almost nothing.

This is not a small effect dressed up. Across the three positions the strongest association with measured bitterness reaches p = 3 x 10^-199, which is many orders of magnitude beyond anything else we publish. It is that large because the variants change the receptor protein directly rather than sitting near a gene and influencing it from a distance. rs713598, rs1726866 and rs10246939 each have their own page.

Two: how your sinuses fight bacteria

The same receptor was found on the apical surface of the sinonasal epithelium — the layer facing the airway, on the cilia that sweep mucus out of your sinuses. It is not there to taste anything. It is there to eavesdrop.

Gram-negative bacteria coordinate with each other by secreting small signalling molecules: each cell releases a signal, and when enough of them are present the population switches on the genes for building a biofilm. Those molecules happen to be shaped like something T2R38 binds. So the receptor detects the bacterial conversation before the bacteria act on it, and answers immediately — a calcium signal, nitric oxide production, faster ciliary beating, and nitric oxide diffusing into the airway fluid where it damages the bacteria directly.

In cultured human sinonasal cells, PAV/PAV strong tasters produced substantially more nitric oxide and killed bacteria more efficiently than AVI/AVI non-tasters (Lee et al., J Clin Invest 2012). The polymorphisms that make the receptor work appear to be involved in susceptibility to upper respiratory infection and to chronic rhinosinusitis that resists treatment (Cohen, Laryngoscope 2017). That is now a page of its own.

Three: whether a child finishes their medicine

The third place is the most ordinary and, in daily life, possibly the most consequential. Many drugs are bitter. How bitter depends on who is tasting them.

In a retrospective analysis of 448 children, those carrying at least one bitter-sensitive allele were more likely to have taken their medication in solid form rather than as a liquid (Lipchock, Reed & Mennella, Clin Ther 2012). Read that the way a parent would: a syrup that tastes unbearable gets refused, and the family finds another way. A later study found the differing bitterness of chloramphenicol and ofloxacin was explained by TAS2R38 diplotype and a TAS2R9 variant respectively (Front Genet 2022).

No guideline chooses a formulation by genotype, and this is not dosing advice. It is an explanation for a real difficulty that is usually filed under a child being difficult.

Why we bothered joining these

Because separately, each of these is a curiosity. Together they are the argument for how this site is built.

Variants live in one excellent public database. Diseases live in another. Prescribing guidelines live in a third, and the genetics of smell and taste in a fourth. Every one of them is good, and none of them are joined to the others. So the fact that one bitter receptor reaches a vegetable, a sinus infection and a refused antibiotic is true in the literature and invisible in practice — you would have to already know it to find it.

MyGeneLog is that join. On rs713598 you can now see all three edges from the position itself: the conditions it is linked to, the drug page it reaches, and the sense it changes. It is the first variant on the site to reach all three at once, and it will not be the last.

The reference is free and open, there is no account, and the desktop app reads your genome file on your own machine without uploading anything. If you want to see where your own copy of this receptor falls, the smell and taste section is the place to start — and unusually for genetics, you can check the answer against your own experience the next time someone hands you a plate of brussels sprouts.

Sources

• Lee RJ et al. T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection. J Clin Invest 2012;122:4145-59 (PMID 23041624)
• Cohen NA. The genetics of the bitter taste receptor T2R38 in upper airway innate immunity and implications for chronic rhinosinusitis. Laryngoscope 2017;127:44-51 (PMID 27650657)
• Lipchock SV, Reed DR, Mennella JA. Relationship between bitter-taste receptor genotype and solid medication formulation usage among young children. Clin Ther 2012;34:728-33 (PMID 22440514)
• Variation in TAS2R receptor genes explains differential bitterness of two common antibiotics. Front Genet 2022;13:960154 (PMID 35967977)
• Bivariate genome-wide association analysis of bitter taste perception. BMC Genomics 2018 (PMID 30223776)