Distribution of TAS2R38 bitter taste receptor phenotype and haplotypes among COVID-19 patients

Abstract

Bitter taste receptor TAS2R38 is expressed in the respiratory tract and can respond to quorum-sensing molecules produced by pathogens, stimulating the release of nitric oxide, with biocidal activity. TAS2R38 presents two main high-frequency haplotypes: the “taster” PAV and the “non-taster” AVI. Individuals carrying the AVI allele could be at greater risk of infections, including SARS-CoV-2. The aim of this study was to assess the frequency of PAV and AVI alleles in COVID-19 patients with severe or non-severe symptoms compared to healthy subjects to further corroborate, or not, the hypothesis that the PAV allele may act as a protecting factor towards SARS-CoV-2 infection while the AVI one may represent a risk factor. After careful selection, 54 individuals were included in the study and underwent genetic analysis and PROP phenotype assessment. Our investigation could not point out at a significant relationship between single nucleotide polymorphisms responsible for PROP bitterness and presence/severity of SARS-CoV-2 infection, as previous studies suggested. Our results uncouple the direct genetic contribution of rs10246939, rs1726866 and rs713598 on COVID-19, calling for caution when proposing a treatment based on TAS2R38 phenotypes.

TAS2R38 haplotypes, COVID-19 infection, and symptomatology: a cross-sectional analysis of data from the Canadian Longitudinal Study on Aging

“…PROP “taster” vs. “non-taster” phenotype was assessed using cotton swabs dipped in PROP solution and was shown to be strongly associated with the TAS2R38 haplotypes. Neither PROP phenotype nor TAS2R38 haplotype was associated with the presence or the severity of COVID-19 infection 13 . Methodological differences in the assessments of COVID-19 outcomes and phenotype/genotypes, and/or sociodemographic characteristics of the participants (as well as substantially different sample sizes) likely contribute to the different observations between these two prior studies.…”

“…Individuals exhibiting the “non-taster” T2R38 phenotype were more likely to be infected with COVID-19 than “taster” phenotypes and experience severe symptomatology. However, such associations were not observed in a smaller cross-sectional study conducted by Risso et al, who reported that COVID-19 outcomes did not differ according to PAV or AVI TAS2R38 haplotypes or PROP “taster” and “non-taster” phenotypes 13 . In addition, to our knowledge, genome-wide association studies (GWAS) of COVID-19 infection, severity, and symptomatology have not reported TAS2R38 as a locus of interest 14 – 16 .…”

“…A previous study showed that sinonasal epithelial cells cultured from PAV homozygotes had higher NO release along with faster ciliary beating frequency and mucociliary clearance compared to cells cultured from AVI homozygotes 9 . Furthermore, the role of TAS2R38 in innate immunity in response to pathogens of the respiratory tract may be supported by recently reported associations between TAS2R38 haplotypes (or T2R38 phenotypes) and coronavirus disease 2019 (COVID-19) infection and symptoms, although evidence is mixed 10 – 13 .…”

Clinical Associations of Bitter Taste Perception and Bitter Taste Receptor Variants and the Potential for Personalized Healthcare

“…Contrarily, a more recent study by Risso et al found no relationship between the TAS2R38 SNPs and severity of COVID-19 symptoms. 116…”

The Bittersweet Symphony of COVID-19: Associations between TAS1Rs and TAS2R38 Genetic Variations and COVID-19 Symptoms

“…In humans, there are two predominant high-frequency TAS2R38 gene haplotypes, determined by three single-nucleotide polymorphisms (SNPs) (i.e., rs713598, rs1726866, and rs1024693) [19]: (i) the proline-alanine-valine (PAV) haplotype, encoding the functional TAS2R38, and the (ii) alanine-valine-isoleucine (AVI) haplotype, encoding the non-functional variant of TAS2R38 [13]. These haplotypes dictate the phenotypic variability in phenylthiocarbamide (PTC) and propylthiouracil (PROP) taste sensitivity, enabling classification of the worldwide population as (i) supertasters (homozygous PAV/PAV individuals); (ii) tasters who perceive different levels of bitter intensity correlating with the relative expression levels of PAV and AVI alleles; (iii) nontasters (homozygous AVI/AVI subjects) [20].…”