Allele specific expression of TAS2R38 in human taste and nasal tissue

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DESCRIPTION (provided by applicant): The human taste system may provide a window on human health. We have recently demonstrated that the bitter taste receptor T2R38 is expressed in the upper airway and is activated by acyl-homoserine lactones (AHLs): quorum-sensing molecules secreted by Pseudomonas aeruginosa and other gram-negative bacteria. Furthermore, we found that T2R38 regulates human upper airway innate defenses through nitric oxide (NO) production, which stimulates mucociliary clearance and has direct antibacterial effects. Moreover, common polymorphisms of the TAS2R38 gene which confer functionality of the receptor, correlate with taste sensitivity to the molecule PTC are linked to significant differences in the ability of upper respiratory cells to clear and kill bacteria in response to AHL. There are three common genotypes for this gene, homozygous dominant, homozygous recessive and heterozygotes. The greatest degree of variability in both PTC taste perception and AHL induced respiratory defense are found in the heterozygote population. Our hypothesis is that allele specific expression of the TAS2R38 polymorphisms predict its function in taste and sinonasal tissue. To test this hypothesis we will collect fungiform taste and sinonasal tissue from 25 heterozygote patients undergoing sinonasal surgery for use in two specific aims: (1) to assess allele specific expression from the sinonasal epithelium and determine whether this persists as the cells are grown in vitro as air liquid interface cultures and correlates to AHL induced respiratory defenses and (2) assess allele specific expression in the fungiform papillae and determine whether it correlates with PTC bitter taste perception and the allele specific expression in the nose. The goal of these aims is to better understand the relationship of the functional and non-functional variants of the TAS2R38 gene in two distinct systems, taste and respiratory defense, and determine whether taste perception can be used clinically to predict severity of airway infection.