Bitter taste receptors (T2Rs, encoded by TAS2R genes) are expressed in various tissues, including the mucosal and bronchial epithelium and immune cells, where they play a crucial role in the early response to pathogens. Research on single nucleotide polymorphisms (SNPs) in TAS2Rs has focused on TAS2R38, while other TAS2R genes and pseudogenes remain largely unexplored.

This thesis investigated SNPs in 25 TAS2R genes and 12 TAS2R pseudogenes in individuals of European ancestry within the Canadian Longitudinal Study on Aging (CLSA). The first part of the thesis compared the allele distribution of TAS2R SNPs with those reported in the 1000 Genomes Project (1KGP) database and examined the association between TAS2R SNPs and self-reported oral health outcomes in the CLSA cohort. The second part assessed the relationship between TAS2R SNPs and COVID-19 infection and antibody seroconversion in individuals with and without at-risk chronic medical conditions, including diabetes, immune-mediated inflammatory disease (IMID), respiratory disease, and cardiovascular disease.

The analyses identified fifteen SNPs in TAS2R8, 9, 13, 14, 20, and 50 as significantly associated with self-reported sore jaw muscles, a symptom commonly linked to temporomandibular disorders (TMDs). TAS2R20 exhibited the highest number of associated SNPs. Structure-function analysis suggested that variants in TAS2R20 may contribute to this symptom by altering ligand interactions. Additionally, in the COVID-19 Questionnaire Study (N = 14,073), rs117458236 (C) in TAS2R20 (OR = 1.95, P = 0.039) was significantly associated with COVID-19 infection. In the COVID-19 Antibody Study (N = 8,313), three SNPs were associated with seroconversion: rs2234235 (G) in TAS2R1 with anti-nucleocapsid (OR = 1.55, P = 0.018) and anti-spike (OR = 0.74, P = 0.033); rs2234010 (A) in TAS2R5 with anti-nucleocapsid (OR = 1.56, P = 0.014); and rs34039200 (A) in TAS2R62P with anti-spike (OR = 0.86, P = 0.013). Subgroup analyses suggested an association between rs2234235 (G) in TAS2R1 and lower odds of spike antibody response, as well as increased risk of SARS-CoV-2 infection among individuals with IMID or respiratory disease.

These findings highlight the potential of TAS2R genetic screening to identify individuals at elevated risk for TMD and COVID-19, suggesting applications in personalized medicine and vaccination strategies for high-risk groups.